TACSTD2

Protein-coding gene in the species Homo sapiens
TACSTD2
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2MAE, 2MVK, 2MVL

Identifiers
AliasesTACSTD2, EGP-1, EGP1, GA733-1, GA7331, GP50, M1S1, TROP2, tumor-associated calcium signal transducer 2, tumor associated calcium signal transducer 2
External IDsOMIM: 137290; MGI: 1861606; HomoloGene: 1763; GeneCards: TACSTD2; OMA:TACSTD2 - orthologs
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for TACSTD2
Genomic location for TACSTD2
Band1p32.1Start58,575,433 bp[1]
End58,577,252 bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for TACSTD2
Genomic location for TACSTD2
Band6|6 C1Start67,511,046 bp[2]
End67,512,780 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr 6: 67.51 – 67.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

This intronless gene 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.[9]

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.[9]

This antigen is the target of sacituzumab govitecan and datopotamab deruxtecan (Dato-DXd),[10] both antibody-drug conjugates.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000184292 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000051397 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Immunomedics Awarded Fast Track Designation by FDA for Sacituzumab Govitecan (IMMU-132) for Triple-Negative Breast Cancer Therapy [1]
  6. ^ Linnenbach AJ, Seng BA, Wu S, Robbins S, Scollon M, Pyrc JJ, et al. (March 1993). "Retroposition in a family of carcinoma-associated antigen genes". Molecular and Cellular Biology. 13 (3): 1507–1515. doi:10.1128/MCB.13.3.1507. PMC 359462. PMID 8382772.
  7. ^ Calabrese G, Crescenzi C, Morizio E, Palka G, Guerra E, Alberti S (Apr 2001). "Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ hybridization". Cytogenetics and Cell Genetics. 92 (1–2): 164–165. doi:10.1159/000056891. PMID 11306819. S2CID 9708614.
  8. ^ a b "Entrez Gene: TACSTD2 tumor-associated calcium signal transducer 2".
  9. ^ a b Vranic S, Gatalica Z (February 2022). "Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers". Bosnian Journal of Basic Medical Sciences. 22 (1): 14–21. doi:10.17305/bjbms.2021.6100. PMC 8860310. PMID 34181512.
  10. ^ Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 Phase III trial[2]

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.


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