UPK1A (Uroplakin 1A)
Uroplakin 1A: A key component of the urothelial plaque, involved in bladder permeability barrier function and associated with bladder cancer and urinary tract infections.
Gene Information Card
| Symbol | UPK1A |
|---|---|
| Full Name | Uroplakin 1A |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 11045 ncbi.nlm.nih.gov/gene/11045 |
| Ensembl ID | ENSG00000105699 |
| UniProt ID | O00322 |
| OMIM ID | 611557 |
| HGNC ID | 12577 |
| Aliases | UPIA, UPIa, Uroplakin Ia |
Description
UPK1A encodes uroplakin 1A, a transmembrane protein that is a major component of the asymmetric unit membrane (AUM) of urothelial plaques. These plaques are essential for the permeability barrier function of the bladder urothelium. UPK1A forms heterodimers with uroplakin 2 (UPK2) and is involved in urothelial differentiation and structural integrity. Mutations and altered expression of UPK1A are associated with bladder cancer, urinary tract infections, and other urothelial disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bladder cancer | Altered UPK1A expression contributes to urothelial dedifferentiation and tumor progression. Loss of uroplakin expression is a marker of invasive bladder cancer. | PubMed: 11592034; COSMIC: UPK1A mutations in bladder carcinoma |
| Urinary tract infection (UTI) | UPK1A is a receptor for uropathogenic E. coli (UPEC) via FimH adhesin, facilitating bacterial colonization and invasion of the urothelium. | PubMed: 11592034; NCBI Gene |
| Urothelial carcinoma in situ | Reduced UPK1A expression correlates with high-grade lesions and poor prognosis. | PubMed: 11592034 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bladder | 28.2 | High |
| Urethra | 15.1 | Medium |
| Kidney | 2.3 | Low |
| Prostate | 1.8 | Low |
| Testis | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| RT4 (bladder carcinoma) | 32.5 | High expression; derived from superficial urothelial cells |
| T24 (bladder carcinoma) | 1.2 | Low expression; invasive phenotype |
| HEK 293 | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.1% (COSMIC) | Likely loss of start codon; predicted loss of function |
| c.205C>T (p.Arg69Cys) | missense | <0.1% (ClinVar) | Uncertain significance; reported in bladder cancer |
| c.388G>A (p.Gly130Ser) | missense | <0.1% (COSMIC) | Unknown effect; somatic in bladder carcinoma |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., start codon loss, frameshift) are predicted to disrupt uroplakin plaque formation, compromising urothelial barrier integrity and potentially promoting bladder cancer progression.
Gain of Function (GOF)
No gain-of-function mutations have been reported for UPK1A.
Dominant Negative (DN)
Dominant-negative effects are not established; however, missense mutations in the transmembrane domain may interfere with heterodimerization with UPK2.
View complete mutation data：
Gene Ontology (GO)
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • structural molecule activity (GO:0005198) | • extracellular exosome (GO:0070062) |
| • epithelial cell differentiation (GO:0030855) | • transport (GO:0006810) |
| • extracellular region (GO:0005576) |
Pathways
• Uroplakin complex assembly (Reactome: R-HSA-2168880)
• Cell junction organization (Reactome: R-HSA-446728)
• Keratinization (Reactome: R-HSA-6805567)
Protein Summary
Uroplakin 1A (UPK1A) is a 27 kDa transmembrane protein (UniProt O00322) that localizes to the apical plasma membrane of superficial urothelial cells. It forms a heterodimer with uroplakin 2 (UPK2) and assembles into hexameric uroplakin particles that constitute the asymmetric unit membrane (AUM). This structure provides mechanical stability and a permeability barrier to the bladder urothelium. UPK1A also serves as a receptor for uropathogenic E. coli via FimH. Loss of UPK1A expression is a hallmark of invasive bladder cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UPK1A Knockout HEK293 Cell Line | EDJ-KQ7257 | Human | 11045 | Details Get a Quote |
| UPK1A Knockout HeLa Cell Line | EDJ-KQ55556 | Human | 11045 | Details Get a Quote |
| UPK1A Knockout A-549 Cell Line | EDJ-KQ64050 | Human | 11045 | Details Get a Quote |
| UPK1A Knockout HCT 116 Cell Line | EDJ-KQ72500 | Human | 11045 | Details Get a Quote |
