H
IPR030718

Extracellular cadherin domain superfamily

InterPro entry
Short nameEC_dom_sf
Overlapping entries
 
Cadherin-like (IPR002126)

Description

Protocadherin-15 (Pcdh15) belongs to the epsilon subfamily of nonclustered protocadherins. It is a component of the tip-links, the extracellular filaments that connect the tips of stereocilia and gate hair cell mechano-electrical transduction channels in the inner ear
[3]
. Pcdh15 interacts with transmembrane channel-like proteins TMC1 and TMC2, which have been implicated in mechanotransduction in mammalian hair cells
[4]
. Mutations in genes coding for Pcdh15 cause deafness in both mice and humans
[5, 1]
. Pcdh15 plays an important role in hair-bundle morphogenesis
[2]
.

This entry represents an extracellular cadherin (EC) domain which can be found at the N-terminal region of Pcdh15. Pcdh15 features exceptionally long extracellular domains containing 11 ECs
[6]
. These repeats are structurally similar, but not identical in sequence, often featuring linkers with conserved calcium-binding sites that confer mechanical strength to them
[7]
.

References

1.Ames Waltzer deaf mice have reduced electroretinogram amplitudes and complex alternative splicing of Pcdh15 transcripts. Haywood-Watson RJ 2nd, Ahmed ZM, Kjellstrom S, Bush RA, Takada Y, Hampton LL, Battey JF, Sieving PA, Friedman TB. Invest. Ophthalmol. Vis. Sci. 47, 3074-84, (2006). View articlePMID: 16799054

2.Characterization of a new allele of Ames waltzer generated by ENU mutagenesis. Washington JL 3rd, Pitts D, Wright CG, Erway LC, Davis RR, Alagramam K. Hear. Res. 202, 161-9, (2005). View articlePMID: 15811708

3.The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells. Pepermans E, Michel V, Goodyear R, Bonnet C, Abdi S, Dupont T, Gherbi S, Holder M, Makrelouf M, Hardelin JP, Marlin S, Zenati A, Richardson G, Avan P, Bahloul A, Petit C. EMBO Mol Med 6, 984-92, (2014). View articlePMID: 24940003

4.Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. Maeda R, Kindt KS, Mo W, Morgan CP, Erickson T, Zhao H, Clemens-Grisham R, Barr-Gillespie PG, Nicolson T. Proc. Natl. Acad. Sci. U.S.A. 111, 12907-12, (2014). View articlePMID: 25114259

5.Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans. Zheng QY, Yan D, Ouyang XM, Du LL, Yu H, Chang B, Johnson KR, Liu XZ. Hum. Mol. Genet. 14, 103-11, (2005). View articlePMID: 15537665

6.Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction. Sotomayor M, Weihofen WA, Gaudet R, Corey DP. Nature 492, 128-32, (2012). View articlePMID: 23135401

7.A Partial Calcium-Free Linker Confers Flexibility to Inner-Ear Protocadherin-15. Powers RE, Gaudet R, Sotomayor M. Structure 25, 482-495, (2017). View articlePMID: 28238533

Further reading

8. Non-clustered protocadherin. Kim SY, Yasuda S, Tanaka H, Yamagata K, Kim H. Cell Adh Migr 5, 97-105, (2011). View articlePMID: 21173574

GO terms

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