MUC16 (mucin 16, cell surface associated)

2007-10-01   Shantibhusan Senapati , Moorthy P Ponnusamy , Ajay P Singh , Maneesh Jain , Surinder K Batra 

Department of Biochemistry, Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Durham Research center 7005, Omaha, NE 68198-5870, USA (SKB)




Atlas Image
Shows the genomic organization of MUC16 gene.


In the genome, MUC16 is localized in 19p13.2 chromosome and is coded by sequences present within approximatively 179kb of genomic DNA.


As per the present available information, there is a discrepancy regarding the total number of exons present in MUC16 genomic DNA. This discrepancy is due to the absence/presence of some of the genomic sequences (particularly for the repeat regions) in the available genomic databases. The terminal nine exons on both 5 and 3 ends code for the amino- and carboxy-terminal domains of MUC16, respectively. At the same time, it has been proposed that five consecutive exons code for a single repeat unit (SRU) of the central tandem repeat domain.


Atlas Image
Shows the structural organization of CA125/MUC16 protein.


MUC16 protein harbors a central tandem repeat region, N-terminal domain and carboxy terminal domain. The N-terminal domain has 12070 numbers of amino acids rich in serine/threonine residues and accounts for the major O-glycosylation known to be present in CA125. The MUC16 protein back bone is dominated by tandem repeat region, which has more than 60 repeat domains, each composed of 156 amino acids. Though all the individual repeat units are not similar, most of them occur more than once in the sequence.
The repeat units are rich in serine, threonine and proline residues, which are typical for any mucins. Each repeat unit has some homology to the SEA (Sea-urchin sperm protein, Enterokinase and Agrin) module, whose exact biological function is not known.
The epitopes for known anti-CA125 antibodies (OC125 and M11) are thought to be present on a small cysteine ring region present in the tandem-repeat region of MUC16.
The carboxy-terminal domain has 284 aminoacids and can be divided into three different regions: extra cellular, transmembrane and cytoplasmic tail. The extracellular part of the carboxy-terminal domain has many N-glycosylation sites and some O-glycosyaltion sites. Several in silico analyses suggest a putative cleavage site in the extracellular part of carboxy-terminal domain. The MUC16 cytoplasmic tail is 31 amino acids long and has many possible phosphorylation sites.
The phosphorylation of CA125 in WISH cells has been reported by labeling with 32PO43- and immunoprecipitaion analysis but the exact site of phosphorylation is yet to be mapped. Interestingly, CA125 contains a putative tyrosine phosphorylation site (RRKKEGY), which was first recognized in Src family protein. This sequence is conserved in the translated mouse EST (AK003577) that has homology with CA125/MUC16 at the C-terminal end. Recently, it has been shown that MUC16 cytoplasmic tail, which contains a polybasic aminoacid sequence, interacts with cytoskeleton through ERM (ezrin/radixin/moesin) actin-binding proteins.


The expression of MUC16 has been reported in human epithelia of conjunctiva, cornea, middle ear and trachea under normal physiological conditions. MUC16 is also expressed in ovarian carcinoma.


It is a type I membrane-bound protein and due to cleavage gets secreted into the extracellular space. On the ocular surface, MUC16 is expressed on the tips of the microplicae of the ocular surface.


MUC16 provides a disadhesive protective barrier to the ocular epithelial surface. Overexpression of CA125/MUC16 in ovarian cancer indicates its possible role in cancer pathogenesis. Studies have shown that CA125/MUC16 binds to mesothelin and galectin-1, which are overexpressed in ovarian cancer. It has also been shown that mesothelin-MUC16 interaction has significance in adhesion of ovarian cancer cells to mesothelial cells present on the inner wall of the peritoneum and on the surface of other abdominal organs. This cell to cell adhesion may help in ovarian cancer metastasis. It has been proposed that galectin-1 bound to MUC16 may cause apoptosis of T cells, and thus help in the suppression of the host immunity.


Similar to mucin 16 of Pan troglodytes, Canis lupus familiaris, Mus musculus, Rattus norvegicus and Gallus gallus.

Implicated in

Entity name
Ovarian cancer
Epithelial ovarian cancer is the most lethal gynaecologic malignancy in the United States and other parts of the world. In the United States, ovarian cancer accounts for approximately 22,000 new cases and 16,000 deaths occurring every year. The epithelial ovarian carcinomas represent approximately 90% of all types of ovarian malignant neoplasms. Due to lack of specific signs and symptoms of this disease, coupled with lack of reliable screening strategies most patients are diagnosed in the advanced stage of the disease, resulting in low overall cure rates. Ovarian cancer patients are generally treated with surgical resection and subsequent platinum-based chemotherapy. Although, many patients initially respond well to chemotherapy, long term survival remains poor due to eventual tumor recurrence and emergence of drug-resistant disease. Overall, the five year survival rate is 45%.
Since the last 20 years, CA125/MUC16 has been used as a well-established marker for diagnosis of ovarian cancer. It is mostly overexpressed in serous type of ovarian cancers and less likely to be expressed in mucinous tumors. More than 80% of ovarian cancer patients have elevated CA125 level during their treatment period. It has been shown that the disease progression is associated with an increase in serum CA125 level, while a decline in serum CA125 level is associated with response to therapy. In another finding, it has been shown that the trend of serum CA125 level during the first three courses of chemotherapy is a strong forecaster of re-examination findings in patients with ovarian carcinoma at the end of treatment. Interestingly, it has been shown that a normal CA125 level by the end of second or third chemotherapy is strongly linked to the survival of patients in stage 3 or stage 4 conditions. Also, variations in the CA125 value even within the normal range carry useful information regarding prediction of time to treatment failure. Additionally, in patients in stage 1 cancers it has been suggested that CA125 elevations are not related to the tumor mass volume. Recently, the potential of CA125/MUC16 as a therapeutic target has been harnessed by using an armed human antibody (3A5) against MUC16 protein.
There is no experimental evidence in the scientific literature for a role of MUC16 in oncogenesis. However, MUC16 possesses many structural similarities with other membrane bound mucins, like MUC1 and MUC4, which are already shown to be functionally involved in different cancers. Transmembrane mucins are hypothesized to serve as sensors of the external environment and can transduce signals via the post-translational modifications of their cytoplasmic tail. Phosphorylation of MUC16 protein has already been reported. Though the exact interacting partner and the site of phosphorylation are unknown, the presence of potential phosphorylation sites in MUC16 cytoplasmic tail indicates the possible role of MUC16 in downstream signal transduction. Further, it has been shown that MUC16 interacts with galectin-1 and mesothelin and these interactions may have a role in cancer progression.


Pubmed IDLast YearTitleAuthors
178982722007Functions of MUC16 in corneal epithelial cells.Blalock TD et al
168807762006Aberrant expression of MUC4 in ovarian carcinoma: diagnostic significance alone and in combination with MUC1 and MUC16 (CA125).Chauhan SC et al
175104222007Armed antibodies targeting the mucin repeats of the ovarian cancer antigen, MUC16, are highly efficacious in animal tumor models.Chen Y et al
168489082006Methylation mediated silencing of TMS1/ASC gene in prostate cancer.Das PM et al
176046782007MUC16 is produced in tracheal surface epithelium and submucosal glands and is present in secretions from normal human airway and cultured bronchial epithelial cells.Davies JR et al
165000402006Distinct evolution of the human carcinoma-associated transmembrane mucins, MUC1, MUC4 AND MUC16.Duraisamy S et al
147645982004Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16).Maeda T et al
122182962002The CA 125 gene: a newly discovered extension of the glycosylated N-terminal domain doubles the size of this extracellular superstructure.O'Brien TJ et al
126159722003The cancer antigen CA125 represents a novel counter receptor for galectin-1.Seelenmeyer C et al
119206442002Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene.Yin BW et al
113697812001Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16.Yin BW et al

Other Information

Locus ID:

NCBI: 94025
MIM: 606154
HGNC: 15582
Ensembl: ENSG00000181143


dbSNP: 94025
ClinVar: 94025
TCGA: ENSG00000181143


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
O-linked glycosylationREACTOMER-HSA-5173105
O-linked glycosylation of mucinsREACTOMER-HSA-913709
Termination of O-glycan biosynthesisREACTOMER-HSA-977068
Diseases of glycosylationREACTOMER-HSA-3781865
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
Dectin-2 familyREACTOMER-HSA-5621480
Diseases associated with O-glycosylation of proteinsREACTOMER-HSA-3906995
Defective C1GALT1C1 causes Tn polyagglutination syndrome (TNPS)REACTOMER-HSA-5083632
Defective GALNT3 causes familial hyperphosphatemic tumoral calcinosis (HFTC)REACTOMER-HSA-5083625
Defective GALNT12 causes colorectal cancer 1 (CRCS1)REACTOMER-HSA-5083636

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
146761942004Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion.168
170673922006Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors.131
195562442009Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier.85
127342002003Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125.74
190750182009A binding domain on mesothelin for CA125/MUC16.63
193372522009Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts.60
200891722010MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells.57
204975502010Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes.57
214212612011MUC16 (CA125) regulates epithelial ovarian cancer cell growth, tumorigenesis and metastasis.55
206280302010Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen.49


Shantibhusan Senapati ; Moorthy P Ponnusamy ; Ajay P Singh ; Maneesh Jain ; Surinder K Batra

MUC16 (mucin 16, cell surface associated)

Atlas Genet Cytogenet Oncol Haematol. 2007-10-01

Online version: