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UniProtKB/Swiss-Prot entry Q8WXI7


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name MUC16_HUMAN
Primary accession number Q8WXI7
Secondary accession numbers Q6ZQW5 Q96RK2
Integrated into Swiss-Prot on October 31, 2006
Sequence was last modified on March 1, 2003 (Sequence version 2)
Annotations were last modified on    March 18, 2008 (Entry version 36)
Name and origin of the protein
Protein name Mucin-16
Synonyms MUC-16
Ovarian carcinoma antigen CA125
Ovarian cancer-related tumor marker CA125
CA-125
Gene name
Name: MUC16
Synonyms: CA125
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-10431, SEQUENCE REVISION TO N-TERMINUS, TISSUE SPECIFICITY, AND INDUCTION.
DOI=10.1159/000064032; PubMed=12218296 [NCBI, ExPASy, EBI, Israel, Japan]
O'Brien T.J., Beard J.B., Underwood L.J., Shigemasa K.;
"The CA 125 gene: a newly discovered extension of the glycosylated N-terminal domain doubles the size of this extracellular superstructure.";
Tumor Biol. 23:154-169(2002).
[2]
NUCLEOTIDE SEQUENCE [MRNA] OF 10432-22152.
DOI=10.1159/000050638; PubMed=11786729 [NCBI, ExPASy, EBI, Israel, Japan]
O'Brien T.J., Beard J.B., Underwood L.J., Dennis R.A., Santin A.D., York L.;
"The CA 125 gene: an extracellular superstructure dominated by repeat sequences.";
Tumor Biol. 22:348-366(2001).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 8297-22152, PROTEIN SEQUENCE OF 21360-21365 AND 21983-21995, AND TISSUE SPECIFICITY.
DOI=10.1074/jbc.M103554200; PubMed=11369781 [NCBI, ExPASy, EBI, Israel, Japan]
Yin B.W.T., Lloyd K.O.;
"Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16.";
J. Biol. Chem. 276:27371-27375(2001).
[4]
SEQUENCE REVISION.
Lloyd K.O., Yin B.W.T.;
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20473-21695.
TISSUE=Uterus;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
PHOSPHORYLATION.
PubMed=9276028 [NCBI, ExPASy, EBI, Israel, Japan]
Fendrick J.L., Konishi I., Geary S.M., Parmley T.H., Quirk J.G. Jr., O'Brien T.J.;
"CA125 phosphorylation is associated with its secretion from the WISH human amnion cell line.";
Tumor Biol. 18:278-289(1997).
[7]
GLYCOSYLATION.
DOI=10.1074/jbc.M302741200; PubMed=12734200 [NCBI, ExPASy, EBI, Israel, Japan]
Kui Wong N., Easton R.L., Panico M., Sutton-Smith M., Morrison J.C., Lattanzio F.A., Morris H.R., Clark G.F., Dell A., Patankar M.S.;
"Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125.";
J. Biol. Chem. 278:28619-28634(2003).
[8]
INTERACTION WITH MSLN.
DOI=10.1074/jbc.M312372200; PubMed=14676194 [NCBI, ExPASy, EBI, Israel, Japan]
Rump A., Morikawa Y., Tanaka M., Minami S., Umesaki N., Takeuchi M., Miyajima A.;
"Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion.";
J. Biol. Chem. 279:9190-9198(2004).
[9]
REVIEW, AND POLYMORPHISM.
DOI=10.1177/1099800404274445; PubMed=15788735 [NCBI, ExPASy, EBI, Israel, Japan]
McLemore M.R., Aouizerat B.;
"Introducing the MUC16 gene: implications for prevention and early detection in epithelial ovarian cancer.";
Biol. Res. Nurs. 6:262-267(2005).
[10]
TISSUE SPECIFICITY.
DOI=10.1167/iovs.05-0735; PubMed=16384952 [NCBI, ExPASy, EBI, Israel, Japan]
Argueso P., Tisdale A., Spurr-Michaud S., Sumiyoshi M., Gipson I.K.;
"Mucin characteristics of human corneal-limbal epithelial cells that exclude the rose bengal anionic dye.";
Invest. Ophthalmol. Vis. Sci. 47:113-119(2006).
Comments
  • FUNCTION: Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces (By similarity).
  • SUBUNIT: Binds to MSLN. Binding to MSLN mediates heterotypic cell adhesion. This may contribute to the metastasis of ovarian cancer to the peritoneum by initiating cell attachment to the mesothelial epithelium via binding to MSLN.
  • SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Secreted, extracellular space. Note=May be liberated into the extracellular space following the phosphorylation of the intracellular C-terminus which induces the proteolytic cleavage and liberation of the extracellular domain.
  • TISSUE SPECIFICITY: Expressed in corneal and conjunctival epithelia (at protein level). Overexpressed in ovarian carcinomas and ovarian low malignant potential (LMP) tumors as compared to the expression in normal ovarian tissue and ovarian adenomas.
  • INDUCTION: Up-regulated in ovarian cancer cells.
  • DOMAIN: Composed of three domains, a Ser-, Thr-rich N-terminal domain, a repeated domain containing more than 60 partially conserved tandem repeats of 156 amino acids each (AAs 12061-21862) and a C-terminal transmembrane contain domain with a short cytoplasmic tail.
  • PTM: Heavily O-glycosylated; expresses both type 1 and type 2 core glycans.
  • PTM: Heavily N-glycosylated; expresses primarily high mannose and complex bisecting type N-linked glycans.
  • PTM: May be phosphorylated. Phosphorylation of the intracellular C-terminal domain may induce proteolytic cleavage and the liberation of the extracellular domain into the extracellular space.
  • PTM: May contain numerous disulfide bridges. Association of several molecules of the secreted form may occur through interchain disulfide bridges providing an extraordinarily large gel-like matrix in the extracellular space or in the lumen of secretory ducts.
  • POLYMORPHISM: The number of repeats is highly polymorphic.
  • MISCELLANEOUS: Antigen that is the basis for a widely used serum assay for the monitoring of patients with ovarian epithelial cancer. Due to lack of sensitivity for stage I disease and lack of specificity, it is of little value in the detection of early ovarian cancer. Due to its similarly elevated levels in some nonmalignant conditions, it is not specific enough to be used for population screening.
  • SIMILARITY: Contains 2 ANK repeats.
  • SIMILARITY: Contains 14 LRR (leucine-rich) repeats.
  • SIMILARITY: Contains 56 SEA domains.
  • WEB RESOURCE: Name=Mucin database; URL="http://www.medkem.gu.se/mucinbiology/databases/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF414442; AAL65133.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF361486; AAK74120.3; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK128681; BAC87568.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_078966.2; -.
UniGene Hs.432676
3D structure databases
SMR Q8WXI7; 21966-22079.
ModBase Q8WXI7.
Organism-specific databases
H-InvDB HIX0080468; -.
HGNC HGNC:15582; MUC16.
GeneLynx MUC16; Homo sapiens.
GenAtlas MUC16.
HPA CAB000004; -.
MIM 606154; gene. [NCBI / EBI]
PharmGKB PA31314; -.
GeneCards Q8WXI7.
Gene expression databases
CleanEx HS_MUC16; -.
Ontologies
GO
GO:0019898; Cellular component: extrinsic to membrane (inferred from direct assay from UniProtKB).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0007155; Biological process: cell adhesion (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR002110; ANK.
IPR000082; SEA.
Graphical view of domain structure.
Pfam PF01390; SEA; 56.
Pfam graphical view of domain structure.
SMART SM00200; SEA; 23.
SMART graphical view of domain structure.
PROSITE PS50297; ANK_REP_REGION; FALSE_NEG.
PS50088; ANK_REPEAT; FALSE_NEG.
PS50024; SEA; 11.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q8WXI7.
Genome annotation databases
Ensembl ENSG00000181143; Homo sapiens. [Contig view]
GeneID 94025; -.
Other
SOURCE MUC16; Homo sapiens.
ProtoNet Q8WXI7.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
ANK repeat; Direct protein sequencing; Glycoprotein; Leucine-rich repeat; Membrane; Phosphoprotein; Polymorphism; Repeat; Secreted; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom     To Length Description FTId
CHAIN   1   22152  22152     Mucin-16. PRO_0000259595
TOPO_DOM   1   22096  22096     Extracellular (Potential). 
TRANSMEM   22097   22117  21     Potential. 
TOPO_DOM   22118   22152  35     Cytoplasmic (Potential). 
REPEAT   7230    7253  24     LRR 1. 
REPEAT   11276   11301  26     LRR 2. 
DOMAIN   12070   12190  121     SEA 1. 
REPEAT   12176   12201  26     LRR 3. 
DOMAIN   12229   12339  111     SEA 2. 
REPEAT   12332   12356  25     LRR 4. 
DOMAIN   12386   12504  119     SEA 3. 
REPEAT   12490   12514  25     LRR 5. 
DOMAIN   12539   12660  122     SEA 4. 
REPEAT   12650   12674  25     LRR 6. 
DOMAIN   12697   12815  119     SEA 5. 
DOMAIN   12853   12971  119     SEA 6. 
DOMAIN   13009   13127  119     SEA 7. 
DOMAIN   13165   13283  119     SEA 8. 
DOMAIN   13315   13439  125     SEA 9. 
DOMAIN   13477   13595  119     SEA 10. 
DOMAIN   13633   13751  119     SEA 11. 
REPEAT   13767   13801  35     ANK 1. 
DOMAIN   13789   13907  119     SEA 12. 
DOMAIN   13939   14063  125     SEA 13. 
DOMAIN   14101   14219  119     SEA 14. 
REPEAT   14209   14232  24     LRR 7. 
DOMAIN   14251   14375  125     SEA 15. 
DOMAIN   14410   14531  122     SEA 16. 
REPEAT   14517   14541  25     LRR 8. 
DOMAIN   14567   14689  123     SEA 17. 
DOMAIN   14723   14845  123     SEA 18. 
REPEAT   14835   14858  24     LRR 9. 
DOMAIN   14877   15001  125     SEA 19. 
DOMAIN   15039   15157  119     SEA 20. 
DOMAIN   15195   15313  119     SEA 21. 
DOMAIN   15348   15469  122     SEA 22. 
DOMAIN   15507   15625  119     SEA 23. 
DOMAIN   15664   15774  111     SEA 24. 
REPEAT   15771   15795  25     LRR 10. 
DOMAIN   15812   15936  125     SEA 25. 
REPEAT   15922   15946  25     LRR 11. 
DOMAIN   16123   16247  125     SEA 26. 
REPEAT   16233   16257  25     LRR 12. 
DOMAIN   16279   16403  125     SEA 27. 
DOMAIN   16437   16559  123     SEA 28. 
REPEAT   16545   16570  26     LRR 13. 
DOMAIN   16591   16715  125     SEA 29. 
REPEAT   16701   16725  25     LRR 14. 
DOMAIN   16750   16871  122     SEA 30. 
DOMAIN   16905   17027  123     SEA 31. 
DOMAIN   17065   17183  119     SEA 32. 
DOMAIN   17221   17339  119     SEA 33. 
DOMAIN   17378   17488  111     SEA 34. 
DOMAIN   17534   17644  111     SEA 35. 
DOMAIN   17689   17807  119     SEA 36. 
DOMAIN   18001   18119  119     SEA 37. 
DOMAIN   18313   18431  119     SEA 38. 
DOMAIN   18625   18743  119     SEA 39. 
REPEAT   18915   18949  35     ANK 2. 
DOMAIN   18937   19055  119     SEA 40. 
DOMAIN   19243   19367  125     SEA 41. 
DOMAIN   19555   19679  125     SEA 42. 
DOMAIN   19866   19990  125     SEA 43. 
DOMAIN   20184   20302  119     SEA 44. 
DOMAIN   20340   20458  119     SEA 45. 
DOMAIN   20496   20614  119     SEA 46. 
DOMAIN   20652   20770  119     SEA 47. 
DOMAIN   20804   20926  123     SEA 48. 
DOMAIN   20964   21082  119     SEA 49. 
DOMAIN   21117   21238  122     SEA 50. 
DOMAIN   21273   21394  122     SEA 51. 
DOMAIN   21433   21542  110     SEA 52. 
DOMAIN   21565   21683  119     SEA 53. 
DOMAIN   21717   21826  110     SEA 54. 
DOMAIN   21836   21957  122     SEA 55. 
DOMAIN   21959   22080  122     SEA 56. 
COMPBIAS   14   12085  12072     Thr-rich. 
COMPBIAS   1638    3055  1418     Ser-rich. 
COMPBIAS   3961    4385  425     Ser-rich. 
COMPBIAS   7085   10395  3311     Ser-rich. 
CARBOHYD   139     139        N-linked (GlcNAc...) (Potential). 
CARBOHYD   434     434        N-linked (GlcNAc...) (Potential). 
CARBOHYD   787     787        N-linked (GlcNAc...) (Potential). 
CARBOHYD   930     930        N-linked (GlcNAc...) (Potential). 
CARBOHYD   957     957        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1375    1375        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1633    1633        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1840    1840        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1877    1877        N-linked (GlcNAc...) (Potential). 
CARBOHYD   1890    1890        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2345    2345        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2375    2375        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2737    2737        N-linked (GlcNAc...) (Potential). 
CARBOHYD   3086    3086        N-linked (GlcNAc...) (Potential). 
CARBOHYD   3179    3179        N-linked (GlcNAc...) (Potential). 
CARBOHYD   3502    3502        N-linked (GlcNAc...) (Potential). 
CARBOHYD   4222    4222        N-linked (GlcNAc...) (Potential). 
CARBOHYD   4500    4500        N-linked (GlcNAc...) (Potential). 
CARBOHYD