Reviewed, UniProtKB/Swiss-Prot Q8WXI7 (MUC16_HUMAN)

Names and origin

Protein names

Recommended name:
    Mucin-16
      Short name=MUC-16
Alternative name(s):
    Ovarian carcinoma antigen CA125
    Ovarian cancer-related tumor marker CA125
      Short name=CA-125

Gene names

Name:	MUC16
Synonyms:	CA125

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	22152 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces By similarity.
Subunit structure	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.
Post-translational modification	Heavily O-glycosylated; expresses both type 1 and type 2 core glycans. Heavily N-glycosylated; expresses primarily high mannose and complex bisecting type N-linked glycans. 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. 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.
Sequence similarities	Contains 2 ANK repeats. Contains 14 LRR (leucine-rich) repeats. Contains 56 SEA domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	ANK repeat Leucine-rich repeat Repeat Transmembrane
PTM	Glycoprotein Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Ref.8 Non-traceable author statement. Source: UniProtKB
Cellular component	extrinsic to membrane Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 22152	22152	Mucin-16
Regions
	Topological domain	1 – 22096	22096	Extracellular Potential
	Transmembrane	22097 – 22117	21	Potential
	Topological domain	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