PCDHA4 explained

Protocadherin alpha-4 is a protein that in humans is encoded by the PCDHA4 gene.^{[1] [2] [3]}

This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.

Further reading

• Yagi T, Takeichi M . Cadherin superfamily genes: functions, genomic organization, and neurologic diversity . Genes Dev. . 14 . 10 . 1169–80 . 2000 . 10817752 . 10.1101/gad.14.10.1169. 44844497 . free .
• Nollet F, Kools P, van Roy F . Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members . J. Mol. Biol. . 299 . 3 . 551–72 . 2000 . 10835267 . 10.1006/jmbi.2000.3777 .
• Senzaki K, Ogawa M, Yagi T . Proteins of the CNR family are multiple receptors for Reelin . Cell . 99 . 6 . 635–47 . 2000 . 10612399 . 10.1016/S0092-8674(00)81552-4 . 14277878 . free .
• Wu Q, Maniatis T . Large exons encoding multiple ectodomains are a characteristic feature of protocadherin genes . Proc. Natl. Acad. Sci. U.S.A. . 97 . 7 . 3124–9 . 2000 . 10716726 . 10.1073/pnas.060027397 . 16203 . free .
• Wu Q, Zhang T, Cheng JF, etal . Comparative DNA Sequence Analysis of Mouse and Human Protocadherin Gene Clusters . Genome Res. . 11 . 3 . 389–404 . 2001 . 11230163 . 10.1101/gr.167301 . 311048 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Schmutz J, Martin J, Terry A, etal . The DNA sequence and comparative analysis of human chromosome 5 . Nature . 431 . 7006 . 268–74 . 2004 . 15372022 . 10.1038/nature02919 . 2004Natur.431..268S . 4373053 .
• Stelzl U, Worm U, Lalowski M, etal . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .

Notes and References

1. Wu Q, Maniatis T . A striking organization of a large family of human neural cadherin-like cell adhesion genes . Cell . 97 . 6 . 779–90 . Jul 1999 . 10380929 . 10.1016/S0092-8674(00)80789-8 . 6014717 . free .
2. Sugino H, Hamada S, Yasuda R, Tuji A, Matsuda Y, Fujita M, Yagi T . Genomic organization of the family of CNR cadherin genes in mice and humans . Genomics . 63 . 1 . 75–87 . Apr 2000 . 10662547 . 10.1006/geno.1999.6066 .
3. Web site: Entrez Gene: PCDHA4 protocadherin alpha 4.