Polycystin-1

from Wikipedia, the free encyclopedia
Polycystin-1
Properties of human protein
Mass / length primary structure 4303 amino acids; 460 kDa
Secondary to quaternary structure multipass receptor
Isoforms 3
Identifier
Gene name PKD-1
External IDs
Transporter classification
TCDB 1.A.5.1.1
designation Polycystine cation channel
Occurrence
Homology family PKD1
Parent taxon Euteleostomi
Orthologue
human mouse
Entrez 5310 18763
Ensemble ENSG00000008710 ENSMUSG00000032855
UniProt P98161 O08852
Refseq (mRNA) NM_000296 NM_013630
Refseq (protein) NP_000287 NP_038658
Gene locus Chr 16: 2.08 - 2.13 Mb Chr 17: 24.28 - 24.32 Mb
PubMed search 5310 18763

Schematic representation of polycystin-1 and polycystin-2 on a cell.

Polycystin-1 (PKD1) is a glycoprotein , which in the body of many vertebrates from PKD1 - gene is encoded. It plays an important role in the cystic kidney disease .

construction

Polycystin-1 consists of 4303 amino acids and has a molecular mass of about 460  kDa . Its structure can be divided into three areas:

The extracellular region consists of over 2500 amino acids. They form repeating leucine- rich units, a region of C-type lecithin , 16 immunoglobulin- like repeating regions and four type III fibronectin-related domains.

function

Polycystin-1 plays in the construction of renal tubules ( tubules an important role). Mutations in the PKD1 gene, which codes for polycystin-1, are directly related to the autosomal dominant cystic kidney (ADPKD), the most common life-threatening hereditary disease in humans. A mutation in PKD1 is the cause in 85% of all ADPKD diseases. In the remaining 15%, PKD2, which encodes polycystin-2, is the starting point for ADPKD. Polycystin 1 is multifunctional and most of the functions of the glycoprotein in the organism are still unknown. Among other things, it plays an important role in the maturation of epithelial cells and in maintaining renal epithelial differentiation; likewise in the organization of the structure of the nephrons in the early fetal stage. Participation in cell-cell and cell-matrix interactions has also been demonstrated.

Polycystine-1 contains two leucine-rich repeats (LRR) that are flanked by two cysteine- rich regions. LRRs are found on proteins involved in protein-protein interactions. Polycystine-1 receives few LRRs. Together with other proteins, it forms a horseshoe-shaped structure to bind RNase A. The LRRs of polycystine-1 also modulate the binding to collagen I , fibronectin and laminin . The LRRs obviously have a proliferation- inhibiting effect in the case of binding to laminin , which in turn can cause mislocalizations of membrane proteins and changes in the extracellular matrix .

Together with polycystin-2, polycystin-1 causes the production of calcium-permeable, non-selective cation channels. Together, both proteins play an important role in regulating growth. Polycystin-2 is an important cofactor. This interaction also explains why mutations in one of the two genes (PKD1 or PKD2) can lead to the PKD phenotype .

Polycystin-1, or the PKD1 is, in a number of different tissues expressed . In addition to the kidneys and liver affected by ADPKD, polycystin is also found in the following organs: duodenum , heart , adrenal gland , lungs , testes, and thymus . The content is three times higher in the cerebral cortex than in the kidney. In polycystic kidneys the content of polycystin corresponding mRNA is twice higher than in normal kidneys.

genetics

see main article: PKD1

In humans, polycystin-1 is encoded by the PKD1 gene ( polycystic kidney disease 1 (autosomal dominant) ) on chromosome 16 gene locus p13.3.

Individual evidence

  1. ↑ C. Stayner and J. Zhou: Polycystin channels and kidney disease. In: Trends in Pharmacological Sciences 22, 2001, pp. 543-546. PMID 11698076
  2. ^ S. Rosetti and PC Harris: Genotype-Phenotype Correlations in Autosomal Dominant and Autosomal Recessive Polycystic Kidney Disease. In: J Am Soc Nephrol 18, 2007, pp. 1374-1380. PMID 17429049
  3. ^ J. Hughes et al: The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. In: Nature Genetics 10, 1995, pp. 151-160. PMID 7663510
  4. ↑ EC cap: Molecular biological studies on the PKD1 gene in cats. Dissertation, Justus Liebig University Giessen, 2008.
  5. ↑ TC Burn et al: Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. The American PKD1 Consortium (APKD1 Consortium). In: Hum. Mol. Genet. 4, 1995, pp. 575-582. PMID 7633406
  6. ↑ AK Bhunia et al .: PKD1 induces p21 (waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. In: Cell 109, 2002, pp. 157-168. PMID 12007403
  7. ↑ CJ Ward et al .: Polycystin, the polycystic kidney disesae 1 protein, is expressed by epithelial cells in fetal, adult and polycystic kidney. In: PNAS 93, 1996, pp. 1524-1528. PMID 8643665
  8. ↑ genenames.org: PKD 1 , accessed on September 10, 2008.

literature