Fibrocystin

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Fibrocystin
Properties of human protein
Mass / length primary structure 4051 amino acids; 444 kDa
Secondary to quaternary structure single pass receptor
Isoforms 2
Identifier
Gene name PKHD1
External IDs
Occurrence
Parent taxon Terrestrial vertebrates
Orthologue
human mouse
Entrez 5314 241035
Ensemble ENSG00000170927 ENSMUSG00000043760
UniProt Q8TCZ9 Q8CIS7
Refseq (mRNA) NM_138694 NM_153179
Refseq (protein) NP_619639 NP_694819
Gene locus Chr 6: 51.59 - 52.06 Mb Chr 1: 20.05 - 20.61 Mb
PubMed search 5314 241035

Fibrocystin (abbreviation: FCYT ; also Polyduction called) is a transmembrane protein , which in the body of many vertebrates from PKHD1 - gene encoding will. It plays an important role in the clinical picture of autosomal - recessive polycystic kidney disease (ARPKD), but also in bile cysts , fibrosis or hyperplasia of the bile duct .

Structure and occurrence

Fibrocystin consists of 4074 amino acids and has a molar mass of 447  kDa .

The rather large polypeptide consists of three sections:

  1. An extracellular N-terminus of 3858 amino acids,
  2. a transmembrane domain and
  3. a short C-terminus

The extracellular area is subdivided into six immunoglobulin- like plexin - transcription factor domains (IPT).

In 2002, CJ Ward and colleagues discovered the gene coding for fibrocystin in the rat animal model . Fibrocystin is in fetal and adult kidney and pancreas expressed , especially in the epithelium . It cannot be detected in other organs and tissues. In the kidneys of PCK rats, a model organism for ARPKD, fibrocystin is expressed much less strongly, but can still be detected.

function

Together with polycystin-2 , fibrocystin is found in the basal body of the primary cilia . In the apical domain of polarized epithelial cells, it is apparently involved in the formation of the tubules and / or the maintenance of the architecture of the lumen of the collecting tube .

genetics

see main article: PKHD1

In humans, fibrocystin is encoded by the PKHD1 gene ( polycystic kidney and hepatic disease 1 ) on chromosome 6 gene locus p21.1-p12.

Mutations in PKHD1 can lead to functional disorders of the fibrocystin gene product and thus lead to the phenotype of ARPKD.

Individual evidence

  1. ↑ James R Davenport, Bradley K Yoder: An incredible decade for the primary cilium: a look at a once-forgotten organelle . In: Am J Physiol Renal Physiol . 289, No. 6, 2005, pp. F1159-1169. doi : 10.1152 / ajprenal.00118.2005 . PMID 16275743 .
  2. ↑ CJ Ward et al: Cellular and subcellular localization of the ARPKD protein; fibrocystin is expressed on primary cilia. In: Human Molecular Genetics , 12, 2003, pp. 2703-2710. PMID 12925574
  3. ↑ CJ Ward et al: The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. In: Nature Genetics 30, 2002, pp. 259-269. PMID 11919560
  4. ↑ MZ Zhang et al .: PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells. In: Proc Nat Acad Sci 101, 2004, pp. 2311-2316. PMID 14983006
  5. ↑ LM Guay-Woodford: The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling. In: Am J Hum Genet 56, 1995, pp. 1101-1107. PMID 7726165
  6. ↑ genenames.org: PKD 1 accessed on September 19, 2008
  7. ↑ C. Bergmann et al.: PKHD1 mutations in autosomal recessive polycystic kidney disease (ARPKD). In: Hum Mutat 23, 2004, pp. 453-463. PMID 15108277

literature

  • ED Avner et al.: Pediatric Nephrology Lippincott Williams & Wilkins, 2003, ISBN 0-781-73545-9 , pp. 679-680