TACSTD2 (TROP2, tumor-associated calcium signal transducer 2) is a single-pass type I plasma membrane glycoprotein of the EPCAM family. It has a large N-glycosylated extracellular region (containing a thyroglobulin type-1 domain) exposed at the cell surface, a single transmembrane helix, and a short cytoplasmic tail with a phosphoinositide-binding motif and a PKC phosphorylation site. TROP2 is expressed on epithelial cells, where it localizes to the lateral/basolateral membrane and cell-cell contacts and modulates epithelial cell proliferation, migration, spreading and adhesion; its loss causes gelatinous drop-like corneal dystrophy. It is strongly overexpressed in many carcinomas and is the target of the antibody-drug conjugate sacituzumab govitecan.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:15607035 Systematic identification of hepatocellular proteins interac... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput keratin-associated-protein and viral partners. Reason: GO:0005515 is uninformative about molecular function. The cited interactions are largely sticky high-throughput Y2H hits (KRTAP/LCE proteins) or a viral-protein screen; removal follows the protein-binding policy and does not dispute them. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput keratin-associated-protein and viral partners. Reason: GO:0005515 is uninformative about molecular function. The cited interactions are largely sticky high-throughput Y2H hits (KRTAP/LCE proteins) or a viral-protein screen; removal follows the protein-binding policy and does not dispute them. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput keratin-associated-protein and viral partners. Reason: GO:0005515 is uninformative about molecular function. The cited interactions are largely sticky high-throughput Y2H hits (KRTAP/LCE proteins) or a viral-protein screen; removal follows the protein-binding policy and does not dispute them. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput keratin-associated-protein and viral partners. Reason: GO:0005515 is uninformative about molecular function. The cited interactions are largely sticky high-throughput Y2H hits (KRTAP/LCE proteins) or a viral-protein screen; removal follows the protein-binding policy and does not dispute them. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput keratin-associated-protein and viral partners. Reason: GO:0005515 is uninformative about molecular function. The cited interactions are largely sticky high-throughput Y2H hits (KRTAP/LCE proteins) or a viral-protein screen; removal follows the protein-binding policy and does not dispute them. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Extracellular region (is_active_in), inherited across the EPCAM/TROP clade. Reason: TROP2 is a membrane protein whose large ectodomain faces the extracellular space and can be shed; the functional anchor is the plasma membrane. Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0005576 extracellular region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Extracellular region (ortholog transfer from mouse Trop2). Reason: Reflects the exposed/shed ectodomain; non-core relative to the membrane anchor. Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nucleus (ortholog transfer) - EPCAM-family intracellular domain can translocate to the nucleus after regulated intramembrane proteolysis. Reason: A plausible signaling pool for the cleaved cytoplasmic domain; not demonstrated for human TROP2 and peripheral to the membrane role. |
| GO:0005829 cytosol | TAS PMID:10192395 Identification of the gene responsible for gelatinous drop-l... | MARK AS OVER ANNOTATED | Summary: Cytosol, from the GDLD gene-identification paper. Reason: TROP2 is a single-pass membrane protein; a soluble cytosolic location is not credible. The short cytoplasmic tail faces the cytoplasm but the protein is membrane-anchored. Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane, inherited across the EPCAM/TROP clade. Reason: Core location - TROP2 is a cell-surface single-pass membrane protein. Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence localizes TROP2 to the plasma membrane. Reason: Core location. Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Automated plasma membrane annotation. Reason: Core location. Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0005923 bicellular tight junction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Bicellular tight junction (is_active_in), inherited (EPCAM P16422). Reason: EPCAM-family members localize to epithelial cell-cell junctions; a polarized location, peripheral to the general plasma-membrane role. |
| GO:0007601 visual perception | TAS PMID:10192395 Identification of the gene responsible for gelatinous drop-l... | MARK AS OVER ANNOTATED | Summary: Visual perception, from the GDLD corneal dystrophy paper. Reason: TROP2 loss causes corneal amyloidosis that impairs vision, but TROP2 does not perform the work of visual perception; this is a disease consequence, not participation in the process. Supporting Evidence: PMID:10192395 gelatinous drop-like corneal dystrophy |
| GO:0009925 basal plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Basal plasma membrane (ortholog transfer). Reason: Epithelial-polarity subdomain location; non-core. |
| GO:0009925 basal plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Basal plasma membrane by similarity. Reason: Polarity subdomain; non-core. |
| GO:0010633 negative regulation of epithelial cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of epithelial cell migration (ortholog transfer). Reason: A modulatory role of TROP2 in epithelia; non-core. |
| GO:0010633 negative regulation of epithelial cell migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of epithelial cell migration by similarity. Reason: Modulatory role; non-core. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Generic membrane. Reason: Correct but general; the specific location is the plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0016020 membrane | TAS PMID:8382772 Retroposition in a family of carcinoma-associated antigen ge... | MODIFY | Summary: Generic membrane (TAS). Reason: Too general; TROP2 is a plasma membrane protein. Proposed replacements: plasma membrane Supporting Evidence: file:human/TACSTD2/TACSTD2-uniprot.txt Membrane; Single-pass type I membrane protein |
| GO:0016323 basolateral plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Basolateral plasma membrane (is_active_in), inherited (EPCAM P16422). Reason: Epithelial-polarity subdomain location; non-core. |
| GO:0016328 lateral plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Lateral plasma membrane (is_active_in), inherited. Reason: TROP2 localizes to lateral membrane/cell-cell contacts in epithelia; a polarized subdomain. |
| GO:0016328 lateral plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lateral plasma membrane (ortholog transfer). Reason: Polarity subdomain; non-core. |
| GO:0016328 lateral plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Lateral plasma membrane by similarity. Reason: Polarity subdomain; non-core. |
| GO:0050678 regulation of epithelial cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of epithelial cell proliferation (ortholog transfer). Reason: TROP2 modulates epithelial proliferation; a downstream role. |
| GO:0051497 negative regulation of stress fiber assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of stress fiber assembly (ortholog transfer). Reason: Cytoskeletal regulation downstream of TROP2; non-core. |
| GO:0051497 negative regulation of stress fiber assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of stress fiber assembly by similarity. Reason: Downstream cytoskeletal role; non-core. |
| GO:0060675 ureteric bud morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ureteric bud morphogenesis (ortholog transfer from mouse Trop2). Reason: Developmental role in kidney; non-core and not shown for human. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Extracellular exosome - TROP2 detected in parotid exosome proteomics. Reason: Membrane proteins are commonly found in exosomes; a secondary location. Supporting Evidence: PMID:19199708 exosome |
| GO:0090191 negative regulation of branching involved in ureteric bud morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of branching in ureteric bud morphogenesis (ortholog transfer). Reason: Developmental role; non-core. |
| GO:0090191 negative regulation of branching involved in ureteric bud morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of ureteric bud branching by similarity. Reason: Developmental role; non-core. |
| GO:0098609 cell-cell adhesion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cell-cell adhesion, inherited across the EPCAM/TROP clade. Reason: EPCAM-family members participate in homophilic/epithelial cell-cell adhesion; a plausible but incompletely defined role for TROP2, retained as non-core. |
| GO:1900025 negative regulation of substrate adhesion-dependent cell spreading | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of substrate adhesion-dependent cell spreading, inherited. Reason: Modulatory role in cell spreading; non-core. |
| GO:1900025 negative regulation of substrate adhesion-dependent cell spreading | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cell spreading (ortholog transfer). Reason: Modulatory role; non-core. |
| GO:1900025 negative regulation of substrate adhesion-dependent cell spreading | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of cell spreading by similarity. Reason: Modulatory role; non-core. |
| GO:1900028 negative regulation of ruffle assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of ruffle assembly (ortholog transfer). Reason: Cytoskeletal/motility regulation; non-core. |
| GO:1900028 negative regulation of ruffle assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of ruffle assembly by similarity. Reason: Downstream role; non-core. |
| GO:2000146 negative regulation of cell motility | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cell motility (ortholog transfer). Reason: Modulatory role in motility; non-core. |
| GO:2000146 negative regulation of cell motility | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of cell motility by similarity. Reason: Modulatory role; non-core. |
Loading supporting content…
Download this section (compressed HTML)Q: What is the molecular function of TROP2 - does it act as a signaling receptor, an adhesion molecule, or a regulator of another receptor, and through which ectodomain and cytoplasmic-tail interactions?
Q: Is human TROP2 subject to regulated intramembrane proteolysis releasing a nuclear intracellular domain, as reported for EPCAM?
Experiment: Define the TROP2 interactome at the epithelial cell surface by proximity labeling, and test whether its cytoplasmic tail and ectodomain are required for its effects on proliferation and migration.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)