TACSTD2

Tumor-associated calcium signal transducer 2, also known as Trop-2 and as epithelial glycoprotein-1 antigen (EGP-1)^[5] is a protein that in humans is encoded by the TACSTD2 gene.^[6][7][8]

TACSTD2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MAE, 2MVK, 2MVL
Identifiers
Aliases	TACSTD2, EGP-1, EGP1, GA733-1, GA7331, GP50, M1S1, TROP2, tumor-associated calcium signal transducer 2, tumor associated calcium signal transducer 2
External IDs	OMIM: 137290; MGI: 1861606; HomoloGene: 1763; GeneCards: TACSTD2; OMA:TACSTD2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p32.1 Start 58,575,433 bp[1] End 58,577,252 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 C1 Start 67,511,046 bp[2] End 67,512,780 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in palpebral conjunctiva mucosa of pharynx nasal epithelium bronchial epithelial cell amniotic fluid oral cavity gingival epithelium skin of thigh human penis epithelium of nasopharynx Top expressed in corneal stroma lip esophagus skin of back urothelium skin of external ear transitional epithelium of urinary bladder cervix granulocyte skin of abdomen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding signaling receptor activity cadherin binding involved in cell-cell adhesion Cellular component integral component of membrane cytosol lateral plasma membrane membrane plasma membrane integral component of plasma membrane basal plasma membrane extracellular exosome nucleus extracellular space bicellular tight junction Biological process ureteric bud morphogenesis response to stimulus negative regulation of ruffle assembly negative regulation of cell motility cell surface receptor signaling pathway negative regulation of branching involved in ureteric bud morphogenesis cell population proliferation regulation of epithelial cell proliferation negative regulation of stress fiber assembly negative regulation of substrate adhesion-dependent cell spreading negative regulation of epithelial cell migration visual perception cell-cell adhesion positive regulation of stem cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4070 56753 Ensembl ENSG00000184292 ENSMUSG00000051397 UniProt P09758 Q8BGV3 RefSeq (mRNA) NM_002353 NM_020047 RefSeq (protein) NP_002344 NP_064431 Location (UCSC) Chr 1: 58.58 – 58.58 Mb Chr 6: 67.51 – 67.51 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

This intronless gene is located at the short arm of chromosome 1 (1p32.1).^[9] It encodes a carcinoma-associated antigen defined by the monoclonal antibody GA733. This antigen is a member of a family including at least two type I membrane proteins. It transduces an intracellular calcium signal and acts as a cell surface receptor.

Mutations of this gene result in gelatinous drop-like corneal dystrophy, an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness.^[8]

Trop-2 expression was originally described in trophoblasts (placenta) and fetal tissues (e.g., lung). Later, its expression was also described in the normal stratified squamous epithelium of the skin, uterine cervix, esophagus, and tonsillar crypts.^[10]

Trop-2 plays a role in tumor progression by actively interacting with several key molecular signaling pathways traditionally associated with cancer development and progression. Aberrant overexpression of Trop-2 has been described in several solid cancers, such as colorectal, renal, lung, and breast cancers. Trop-2 expression has also been described in some rare and aggressive malignancies, e.g., salivary duct, anaplastic thyroid, uterine/ovarian, and neuroendocrine prostate cancers.^[10] This overexpression is caused by deregulations at a transcriptional and posttranscriptional level.^[9]

Trop-2 causes cancer cell growth, proliferation, invasion, migration, and survival of cancer cells, which leads to Trop-2 being associated with tumor aggressiveness and poor prognosis. This is also confirmed by the fact, that the proliferation of tumor cells is disturbed when Trop-2 is knocked down. These facts make Trop-2 a possible prognostic biomarker to identify high-risk patients, as well as an attractive therapeutic target for late-stage diseases^[9]

This antigen is the target of sacituzumab govitecan and datopotamab deruxtecan (Dato-DXd),^[11] both antibody-drug conjugates.