TACSTD2

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

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) Band 1p32.1 Start 58,575,433 bp End 58,577,252 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6|6 C1 Start 67,511,046 bp End 67,512,780 bp
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
Wikidata
View/Edit Human View/Edit Mouse

This intronless gene is located at the short arm of chromosome 1 (1p32.1). 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.

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.

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. This overexpression is caused by deregulations at a transcriptional and posttranscriptional level.

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

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

Further reading

• Linnenbach AJ, Wojcierowski J, Wu SA, Pyrc JJ, Ross AH, Dietzschold B, et al. (January 1989). "Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733". Proceedings of the National Academy of Sciences of the United States of America. 86 (1): 27–31. Bibcode:1989PNAS...86...27L. doi:10.1073/pnas.86.1.27. PMC 286396. PMID 2911574.
• Fornaro M, Dell'Arciprete R, Stella M, Bucci C, Nutini M, Capri MG, Alberti S (September 1995). "Cloning of the gene encoding Trop-2, a cell-surface glycoprotein expressed by human carcinomas". International Journal of Cancer. 62 (5): 610–618. doi:10.1002/ijc.2910620520. PMID 7665234. S2CID 23260113.
• El Sewedy T, Fornaro M, Alberti S (January 1998). "Cloning of the murine TROP2 gene: conservation of a PIP2-binding sequence in the cytoplasmic domain of TROP-2". International Journal of Cancer. 75 (2): 324–330. doi:10.1002/(SICI)1097-0215(19980119)75:2<324::AID-IJC24>3.0.CO;2-B. PMID 9462726.
• Ripani E, Sacchetti A, Corda D, Alberti S (May 1998). "Human Trop-2 is a tumor-associated calcium signal transducer". International Journal of Cancer. 76 (5): 671–676. doi:10.1002/(SICI)1097-0215(19980529)76:5<671::AID-IJC10>3.0.CO;2-7. PMID 9610724.
• Tsujikawa M, Kurahashi H, Tanaka T, Nishida K, Shimomura Y, Tano Y, Nakamura Y (April 1999). "Identification of the gene responsible for gelatinous drop-like corneal dystrophy". Nature Genetics. 21 (4): 420–423. doi:10.1038/7759. PMID 10192395. S2CID 2275476.
• Nakamura T, Nishida K, Dota A, Adachi W, Yamamoto S, Maeda N, et al. (May 2000). "Gelatino-lattice corneal dystrophy: clinical features and mutational analysis". American Journal of Ophthalmology. 129 (5): 665–666. doi:10.1016/S0002-9394(00)00369-X. PMID 10844062.
• Kinoshita S, Nishida K, Dota A, Inatomi T, Koizumi N, Elliott A, et al. (July 2000). "Epithelial barrier function and ultrastructure of gelatinous drop-like corneal dystrophy". Cornea. 19 (4): 551–555. doi:10.1097/00003226-200007000-00029. PMID 10928776. S2CID 43011710.
• Tsujikawa M, Tsujikawa K, Maeda N, Watanabe H, Inoue Y, Mashima Y, et al. (August 2000). "Rapid detection of M1S1 mutations by the protein truncation test". Investigative Ophthalmology & Visual Science. 41 (9): 2466–2468. PMID 10937555.
• Ha NT, Fujiki K, Hotta Y, Nakayasu K, Kanai A (July 2000). "Q118X mutation of M1S1 gene caused gelatinous drop-like corneal dystrophy: the P501T of BIGH3 gene found in a family with gelatinous drop-like corneal dystrophy". American Journal of Ophthalmology. 130 (1): 119–120. doi:10.1016/S0002-9394(00)00596-1. PMID 11004271.
• Tasa G, Kals J, Muru K, Juronen E, Piirsoo A, Veromann S, et al. (November 2001). "A novel mutation in the M1S1 gene responsible for gelatinous droplike corneal dystrophy". Investigative Ophthalmology & Visual Science. 42 (12): 2762–2764. PMID 11687514.
• Yoshida S, Kumano Y, Yoshida A, Numa S, Yabe N, Hisatomi T, et al. (June 2002). "Two brothers with gelatinous drop-like dystrophy at different stages of the disease: role of mutational analysis". American Journal of Ophthalmology. 133 (6): 830–832. doi:10.1016/S0002-9394(02)01407-1. PMID 12036680.
• Ren Z, Lin PY, Klintworth GK, Iwata F, Munier FL, Schorderet DF, et al. (June 2002). "Allelic and locus heterogeneity in autosomal recessive gelatinous drop-like corneal dystrophy". Human Genetics. 110 (6): 568–577. doi:10.1007/s00439-002-0729-z. PMID 12107443. S2CID 24052349.
• Ha NT, Chau HM, Cung LE, Thanh TK, Fujiki K, Murakami A, Kanai A (March 2003). "A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy". American Journal of Ophthalmology. 135 (3): 390–393. doi:10.1016/S0002-9394(02)01952-9. PMID 12614764.
• Gires O, Eskofier S, Lang S, Zeidler R, Münz M (2003). "Cloning and characterisation of a 1.1 kb fragment of the carcinoma-associated epithelial cell adhesion molecule promoter". Anticancer Research. 23 (4): 3255–3261. PMID 12926061.
• Tian X, Fujiki K, Li Q, Murakami A, Xie P, Kanai A, et al. (March 2004). "Compound heterozygous mutations of M1S1 gene in gelatinous droplike corneal dystrophy". American Journal of Ophthalmology. 137 (3): 567–569. doi:10.1016/j.ajo.2003.08.008. PMID 15013888.
• Murakami A, Kimura S, Fujiki K, Fujimaki T, Kanai A (2004). "Mutations in the membrane component, chromosome 1, surface marker 1 (M1S1) gene in gelatinous drop-like corneal dystrophy". Japanese Journal of Ophthalmology. 48 (4): 317–320. doi:10.1007/s10384-003-0064-5. PMID 15295654. S2CID 28358081.