LY6K (lymphocyte antigen 6 complex locus K) is a GPI-anchored member of the Ly6/uPAR family with a snake-toxin-like three-finger fold. It is normally a cancer-testis antigen expressed in testis, where the mouse ortholog is required for sperm migration into the oviduct and for sperm binding to the zona pellucida, acting in a complex with the GPI-anchored protein TEX101. The mature protein is attached to the extracellular leaflet of the plasma membrane by a GPI anchor (partitioning into membrane rafts) and is also found in the sperm acrosome. LY6K is aberrantly re-expressed in non-small-cell lung and esophageal squamous cell carcinomas, where it promotes cancer cell growth and a shed/soluble form serves as a serum tumor biomarker.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001669 acrosomal vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: LY6K is present in the sperm acrosome. Reason: In testis/sperm LY6K localizes to the acrosomal secretory vesicle, consistent with its role in sperm function; supported by the mouse ortholog and family IBA. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:Q9CWP4}. |
| GO:0001669 acrosomal vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: LY6K is present in the sperm acrosome. Reason: In testis/sperm LY6K localizes to the acrosomal secretory vesicle, consistent with its role in sperm function; supported by the mouse ortholog and family IBA. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:Q9CWP4}. |
| GO:0001669 acrosomal vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: LY6K is present in the sperm acrosome. Reason: In testis/sperm LY6K localizes to the acrosomal secretory vesicle, consistent with its role in sperm function; supported by the mouse ortholog and family IBA. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Cytoplasmic vesicle, secretory vesicle, acrosome {ECO:0000250|UniProtKB:Q9CWP4}. |
| GO:0005576 extracellular region | EXP PMID:18089789 Cancer-testis antigen lymphocyte antigen 6 complex locus K i... | KEEP AS NON CORE | Summary: A soluble/shed form of LY6K is detectable in serum. Reason: LY6K is primarily a GPI-anchored surface protein; it is released into the extracellular space (detected in serum as a cancer biomarker and reported secreted), which is a secondary form of a membrane protein. Supporting Evidence: PMID:18089789 We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A soluble/shed form of LY6K is detectable in serum. Reason: LY6K is primarily a GPI-anchored surface protein; it is released into the extracellular space (detected in serum as a cancer biomarker and reported secreted), which is a secondary form of a membrane protein. Supporting Evidence: PMID:18089789 We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8940388 | KEEP AS NON CORE | Summary: A soluble/shed form of LY6K is detectable in serum. Reason: LY6K is primarily a GPI-anchored surface protein; it is released into the extracellular space (detected in serum as a cancer biomarker and reported secreted), which is a secondary form of a membrane protein. Supporting Evidence: PMID:18089789 We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC |
| GO:0005737 cytoplasm | EXP PMID:18089789 Cancer-testis antigen lymphocyte antigen 6 complex locus K i... | KEEP AS NON CORE | Summary: A cytoplasmic pool of LY6K is reported in cancer cells. Reason: LY6K is detected in the cytoplasm in overexpressing tumor cells, likely reflecting biosynthetic/secretory transit of this GPI-anchored protein; not its functional surface location. Supporting Evidence: PMID:18089789 Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A cytoplasmic pool of LY6K is reported in cancer cells. Reason: LY6K is detected in the cytoplasm in overexpressing tumor cells, likely reflecting biosynthetic/secretory transit of this GPI-anchored protein; not its functional surface location. Supporting Evidence: PMID:18089789 Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: LY6K is a GPI-anchored protein on the extracellular leaflet of the plasma membrane. Reason: The mature protein carries a C-terminal GPI anchor and is displayed on the cell membrane; this is its functional location, with the three-finger ectodomain exposed extracellularly. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Cell membrane {ECO:0000250|UniProtKB:Q9CWP4}; Lipid-anchor, GPI-anchor |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: LY6K is a GPI-anchored protein on the extracellular leaflet of the plasma membrane. Reason: The mature protein carries a C-terminal GPI anchor and is displayed on the cell membrane; this is its functional location, with the three-finger ectodomain exposed extracellularly. The cell-type-restricted surface context (the sperm plasma membrane, from the mouse ortholog's role in the TEX101 complex and zona binding; LY6K is otherwise a cancer-testis antigen) is carried by the sperm plasma membrane (GO:0097524) core-function location rather than by a generic-term extension. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Cell membrane {ECO:0000250|UniProtKB:Q9CWP4}; Lipid-anchor, GPI-anchor |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8940388 | ACCEPT | Summary: LY6K is a GPI-anchored protein on the extracellular leaflet of the plasma membrane. Reason: The mature protein carries a C-terminal GPI anchor and is displayed on the cell membrane; this is its functional location, with the three-finger ectodomain exposed extracellularly. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Cell membrane {ECO:0000250|UniProtKB:Q9CWP4}; Lipid-anchor, GPI-anchor |
| GO:0007339 binding of sperm to zona pellucida | IBA GO_REF:0000033 | ACCEPT | Summary: LY6K controls binding of sperm to the zona pellucida (mouse ortholog). Reason: Ly6k-deficient mice have impaired sperm migration into the oviduct and defective zona pellucida binding, and LY6K acts in a complex with TEX101; this is the core testis function, transferred by the family IBA. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Required for sperm migration into the oviduct and male fertility by controlling binding of sperm to zona pellucida |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: LY6K partitions into membrane rafts. Reason: GPI-anchored proteins such as LY6K associate with detergent-resistant membrane microdomains; a sub-location of its plasma membrane pool. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Membrane raft {ECO:0000250|UniProtKB:Q9CWP4}. |
| GO:0045121 membrane raft | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: LY6K partitions into membrane rafts. Reason: GPI-anchored proteins such as LY6K associate with detergent-resistant membrane microdomains; a sub-location of its plasma membrane pool. Supporting Evidence: file:human/LY6K/LY6K-uniprot.txt Membrane raft {ECO:0000250|UniProtKB:Q9CWP4}. |
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Download this section (compressed HTML)Q: What is the molecular activity of LY6K in the TEX101 complex, and does its re-expression in carcinomas use the same partner?
Experiment: Define the LY6K interactome at the cancer cell surface versus the sperm surface and test whether its growth-promoting effect in carcinoma cells requires GPI anchoring.
Type: proteomics and structure-function
Deep research (falcon / perplexity-lite) failed; notes from cached publication and UniProt Q17RY6.
Localization conclusion: GPI-anchored plasma membrane (ectodomain exposed on outer leaflet, raft), acrosome in sperm;
shed/soluble form in serum and a cytoplasmic pool in overexpressing tumor cells. Genuinely cell-surface accessible.
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