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Fig. 1. CD44 structure and sequence conservation. (A) Genomic organization of CD44. The human gene encoding CD44 consists of 20 exons and is located at 11p13. The exons encoding the hyaluronan-binding domain and transmembrane domain are cross-hatched and stippled, respectively. (B) mRNA splicing patterns in CD44. The standard form of CD44, CD44s, comprises exons 1-5, 16-18 and 20 (green). Most variant forms of CD44, CD44v, contain the standard exons with combinations of exons 6-15 (v1-v10) (orange). The inclusion of exon 19, normally absent in most CD44 transcripts, results in a CD44 short-tail variant owing to use of an alternative translation stop codon. (C) Cross-species sequence comparison of the CD44 transmembrane and cytoplasmic domains. Orthologous CD44 sequences (human, P16070; Papio hamadryas (baboon), P14745; Mus musculus (mouse), P15379; Rattus norvegicus (rat), P26051; Cricetulus griseus (chinese hamster), P20944; Mesocricetus auratus (golden hamster), Q60522; Canis familiaris (dog), Q28284; Bos taurus (cow), Q29423; Equus caballus (horse), Q05078; Capra hircus(goat), CD051825; Ceratotherium simum simum (rhinoceros), AF045939; Gallus gallus (chicken); AAD37443; Anas platyrhynchos (duck), AAK40246) were aligned using the ClustalW program (EBI). In reference to the human sequence, the identical, physicochemically conserved and non-conserved amino acid residues are shown in blue, yellow and red, respectively. Note that the dog sequence is incomplete. (D) Sequence features of the human CD44 transmembrane and cytoplasmic domains. The transmembrane domain (grey) contains two sites for regulated intramembranous cleavage (arrowheads). Several functional motifs have been identified including a FERM-binding domain (green), ankyrin-binding domain (brown) and a basolateral targeting motif (light blue). Other posttranslational modifications include phosphorylation on serine residues (blue) with a protein kinase C (PKC) site at Ser291, a Ca2+/calmodulin-dependent protein kinase II (CaMKII) site at Ser325, and a predicted protein kinase A (PKA) site at Ser316. Palmitoylation is also known to occur, with prospective sites being Cys286 and Cys295 (orange). The cytoplasmic tail terminates in a potential PDZ-domain-binding peptide (magenta).





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