PDZ-Domain-Binding Sites Are a Common Motif of Protocadherins

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Electronic Supplementary Material

PDZ-domain-binding sites are common among cadherins

Fabio Demontis, Bianca Habermann, and Christian Dahmann

Table S1

Human,  and  protocadherins containing C-terminal sequences matching the consensus sequences for PDZ-domain-binding sites. The C-terminal ten amino acids are shown and the class of the PDZ-domain-binding site is indicated. PDZ-domain-binding site consensus sequences are as shown in Table 1. Note that because orthologs of these protocadherins could not be identified and, therefore, an evolutionary conservation of the PDZ-domain-binding sites could not be assessed, the functional relevance of these putative PDZ-domain-binding sites remains unclear. Hs, Homo sapiens; is., isoform.

Accession numbers

Accession numbers of the Drosophila melanogaster sequences employed in this study are: DN-Cad (CG7100/NP_724073), DN-Cad2 (CG7527/NP_609855), DE-Cad (CG3722/BAA05942), Fat (CG3352/NP_477497), Fat2 (CG7749/NP_649171), Stan/Flamingo (CG11895/NP_724962), Cad74A (CG6445/NP_730261), Cad88C (CG3389/NP_731930), Cad87A (CG6977/NP_731649), Cad99C (CG31009/NP_733314), Dachsous (CG17941/NP_523446), Cad89D (CG14900/NM_142297), Cad86C (CG4509/NP_788635), Cad96Cb (CG10421/NP_733088), Calsyntenin-1 (CG11059/NP_726646), Cad96Ca (CG10244/NP_651349), and Ret (CG14396/NP_724317). Classic catenin-binding sites have been found in DN-cad (Iwai et al., 1997), DN-cad2 (Hill et al., 2001), and DE-cad (Oda et al., 1994).

Anopheles gambiae and Apis mellifera cadherin sequences employed here are: Ag Cad96Ca (XP_320863), Am Cad96Ca (XP_392586), Ag Cad99C (XP_312660), Am Cad99C (XP_396248), and Ag Cad88C (XP_321514). The cytoplasmic regions of Am Cad88C, Ag Fat, and Am Fat were predicted by tBLASTn (http://www.ncbi.nlm.nih.gov/BLAST/Genome/Insects.html) using the corresponding full-length Dm sequence as query sequence.

Accession numbers of the human sequences employed in this study are: Cadherin 1 (NP_004351), Cadherin 2 (NP_001783), Cadherin 3 (NP_001784), Cadherin 4 (NP_001785), Cadherin 5 (NP_001786), Cadherin 6 (NP_004923), Cadherin 7 (NP_004352), Cadherin 8 (NP_001787), Cadherin 9 (NP_057363), Cadherin 10 (NP_006718), Cadherin 11 is.1 (NP_001788), is.2 (NP_387513), with is. = isoform, Cadherin 12 (NP_004052), Cadherin 15 (NP_004924), Cadherin 16 (NP_004053), Cadherin 17 (NP_004054), Cadherin 18 (NP_004925), Cadherin 19 (NP_066976), Cadherin 20 (NP_114097), Cadherin 22 (NP_067071), Cadherin 23 is.1 (NP_071407), is.2 (NP_443068), Cadherin 24 (Q86UP0), Cadherin-like 26 is.a (NP_817089), is.b (NP_068582), Calsyntenin 1 is.1 (NP_001009566), is.2 (NP_055759), Calsyntenin 2 (NP_071414), Calsyntenin 3 (NP_055533), Dachsous 2, is.1 (NP_060109), is.2 (NP_955380), Fat 1 (NP_005236), Fat 2 (NP_001438), Fat 3 (BAB86868), Fat 4 (NP_078858), Flamingo 1 (Q9NYQ7), Flamingo 2 (NP_055061), Flamingo 3 (NP_001398), Protocadherin LKC (NP_060145), Mu-Protocadherin is.1 (NP_068743), is.2 (NP_060187), is.3 (NP_112554), Ret is.a (NP_066124), is.c (NP_065681), hypothetical protein FLJ23834 (NP_689963), Desmocollin 1 is.a (NP_077739), is.b (NP_004939), Desmocollin 2 is.a (NP_077740), is.b (NP_004940), Desmocollin 3 is.a (NP_001932), is.b (NP_077741), Desmoglein 1 (NP_001933), Desmoglein 2 (NP_001934), Desmoglein 3 (NP_001935), Desmoglein 4 (NP_817123), Protocadherin 1 is.1 (NP_002578), is.2 (NP_115796), Protocadherin 7 is.a (NP_002580), is.b (NP_115832), is.c (NP_115833), Protocadherin 8 is.1 (NP_002581), is.2 (NP_116567), Protocadherin 9 is.1 (NP_982354), is.2 (NP_065136), Protocadherin 10 is.1 (NP_116586), is.2 (NP_065866), Protocadherin 11 X-linked is.a (NP_055337), is.b (NP_116749), is.c (NP_116750), is.d (NP_116751), Protocadherin 11 Y-linked is.a (NP_116753), is.b (NP_116754), is.c (NP_116755), Protocadherin 12 (NP_057664), Protocadherin 15 (NP_149045), Dachsous 1 (NP_003728), Protocadherin 17 (NP_055274), Protocadherin 18 (NP_061908), Protocadherin 19 (XP_033173), Protocadherin 20 (NP_073754), Protocadherin 21 (NP_149091), Protocadherin psi1 (AAK51618), Protocadherin psi2 (AAK51611), Protocadherin  1, is.1 (NP_061723), is.2 (NP_113598), is.3 (NP_113599), 2 is.1 (NP_061728), is.2 (NP_113683), is. 3 (NP_113684), 3 is.1 (NP_061729), is.2 (NP_113685), 4 is.1 (NP_061730), is. 2 (NP_113688), 5 is.1 (NP_061731), is.2 (NP_113689), 6 is.1 (NP_061732), is.2 (NP_114036), is.3 (NP_114037), 7 is.1 (NP_061733), is. 2 (NP_114040), 8 is.1 (NP_061734), is.2 (NP_114062), 9 is.1 (NP_114063), is.2 (NP_054724), 10 is.1 (NP_061724), is.2 (NP_114065), is.3 (NP_114066), 11 is.1 (NP_061725), is.2 (NP_114067), 12 is.1 (NP_061726), is.2 (NP_114070), 13 is.1 (NP_061727), is.2 (NP_114071), C1 is.1 (NP_061721), is.2 (NP_114088), C2 is.1 (NP_061722), is.2 (NP_114089), Protocadherin  1 (AAD43749), 2 (AAD43756), 3 (AAD43757), 4 (AAD43759), 5 (AAK51620), 6 (AAD43760), 7 (AAD43761), 8 (AAD43762), 9 (AAD43763), 10 (AAD43750), 11 (AAD43751), 12 (AAD43752), 13 (AAD43753), 14 (AAD43754), 15 (AAD43755), 16 (NP_066008), Protocadherin  subfamily A, 1 is.1 (NP_061735), is.2 (NP_114382), 2 is.1 (NP_061738), is.2 (NP_114398), 3 is.1 (NP_061739), is.2 (NP_114400), 4 is.1 (NP_061740), is.2 (NP_114442), 5 is.1 (NP_061741), is.2 (NP_114443), 6 is.1 (NP_061742), is.2 (NP_114475), 7 is.1 (NP_061743), is.2 (NP_114476), 8 is.1 (NP_114477), is.2 (NP_054723), 9 is.1 (NP_061744), is.2 (NP_114478), 10 is.1 (NP_061736), is.2 (NP_114479), 11 is.1 (NP_061737), is.2 (NP_114480), is.3 (NP_114481), 12 is.1 (NP_003726), is.2 (NP_115265), Protocadherin  subfamily B, 1 is.1 (NP_061745), is.2 (NP_115266), 2 is.1 (NP_061746), is.2 (NP_115267), 3 is.1 (NP_061747), is.2 (NP_115268), 4 is.1 (NP_003727), is.2 (NP_115269), 5 is.1 (NP_061748), is.2 (NP_115270), 6 is.1 (NP_061749), is.2 (NP_115271), 7 is.1 (NP_061750), is.2 (NP_115272), Protocadherin  subfamily C, 3 is.1 (NP_002579), 3 is.2 (NP_115778), is.3 (AAH63437), 4 is.1 (NP_061751), is.2 (NP_115782), 5 is.1 (NP_061752), and is.2 (NP_115783).

Catenin-binding sites have been found in human Cadherin 1-12, 15, 18-20, 22, 24, and 26-like, Desmogleins, and Desmocollins (Angst et al., 2001, Hill et al., 2001, Nollet et al., 2000). Cadherin 11 has been counted as not containing a catenin-binding site, even though two distinct alternatively spliced isoforms have been reported, one of which contains a catenin-binding site and the other a PDZ-domain-binding motif (Okazaki et al., 1994). Fat1 contains a cytoplasmic region that is only distantly related to the catenin-binding site (Dunne et al., 1995). Experimental evidence for the binding of Fat1 to a catenin has not been reported and for this analysis we have considered Fat1 as lacking a catenin-binding site. Cadherin 13 was excluded from this analysis as it is GPI-anchored and, thus, lacks a cytoplasmic region (Ranscht and Dours-Zimmermann, 1991).

Accession numbers of the other vertebrate sequences employed in this study are:

Danio rerio Cadherin 23 (NP_999974), Dr Fat1 (NP_998132), Dr Protocadherin 15b (NP_001012504), Tetraodon nigroviridis Protocadherin 1 is.2 (CAG01546), Tn Protocadherin 7 (CAG11168), Tn Dachsous 2 (CAF96583), Tn LKC-cadherin EST (CR718517), Xenopus laevis Protocadherin 8 (AAH74360), Xl Ret (AAG00544), Xl Mu-protocadherin (AAH79708), Xenopus tropicalis protocadherin LKC EST (CX977065), Xt Protocadherin 1 EST (CX839352), Xt Protocadherin 7 EST (CX827206), Mus musculus Protocadherin 8 (AAH53008), Mm Fat2 (CAI52049), Mm Protocadherin  1 (NP_444356), Rattus norvegicus Protocadherin  1 (NP_001014800), M. musculus Protocadherin  13 (NP_444368.1), R. norvegicus Protocadherin  13 (NP_001014803), R. norvegicus Protocadherin  16 (NP_001014804), M. musculus Protocadherin  22 (AAK26073.1), Tetraodon nigroviridis CAF92266 (CAF92266), Xenopus laevis MGC84237 (AAH74360), M. musculus Protocadherin 10 (NP_035173.2).

Other Fugu rubripes, Tetraodon nigroviridis, Danio Rerio, Xenopus laevis, and Xenopus tropicalis cadherin sequences were obtained by tBLASTn analysis of the respective genomes using full-length human cadherin sequences as query.

References

Angst BD, Marcozzi C, Magee AI (2001) The cadherin superfamily: diversity in form and function. J Cell Sci: 114, 629-641

Dunne J, Hanby AM, Poulsom R, Jones TA, Sheer D, Chin WG, Da SM, Zhao Q, Beverley PC, Owen MJ (1995) Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics 30: 207-223

Hill E, Broadbent ID, Chothia C, Pettitt J (2001) Cadherin superfamily proteins in Caenorhabditis elegans and Drosophila melanogaster. J Mol Biol 305: 1011-1024

Iwai Y, Usui T, Hirano S, Steward R, Takeichi M, Uemura T (1997) Axon patterning requires DN-cadherin, a novel neuronal adhesion receptor, in the Drosophila embryonic CNS. Neuron 19: 77-89

Nollet F, Kools P, van Roy F (2000) Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol 299: 551-572

Oda H, Uemura T, Harada Y, Iwai Y, Takeichi M (1994) A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev Biol 165: 716-726

Okazaki M, Takeshita S, Kawai S, Kikuno R, Tsujimura A, Kudo A, Amann E (1994) Molecular cloning and characterization of OB-cadherin, a new member of cadherin family expressed in osteoblasts. J Biol Chem 269: 12092-12098

Ranscht B, Dours-Zimmermann MT (1991) T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region. Neuron 7: 391-402