XB-FEAT-988106

adam13

This is the community wiki page for the gene adam13 please feel free to add any information that is relevant to this gene that is not already captured elsewhere in Xenbase.

nomenclature changes

13SEPT2023 Note there is currently a BUG in the curation interface preventing us from updating the summary section gene names and symbols- this will be fixed soon! the gene names have been changed from adam33 to adam13. Once these changes have cascaded through the database, target for MOs, Abs and gRNAs will be accurate. Until then, please use caution when re-using these reagent names, or interpreting target specificity.

13SEPT2023 The Xenopus name for this gene is changing from adam33 to adam13, following review by Xenbase staff and NCBI ref Seq team.

GeneID: 677728 (XB-GENE-988107) should be named ADAM13 rather than ADAM33 along with X. laevis L & S Gene ID: 386623 & Gene ID: 373720.

By synteny, the true Xtropicalis ortholog of human ADAM33 is GeneID: 101732075 (XB-GENE-29085839) along with X. laevis L & S GeneID: 108697349 & GeneID: 108704093.

The nomenclature error occurred because NCBI had a setting that prohibited the ADAM33 symbol from being applied to GeneID: 101732075. These true adam33 genes are represented on XB-GENEPAGE-29085838.

synteny

Xtr.Chr1: LOC100493985 smyd5 loc101734035 LOC100145764 dctn1 geneid:677728; adam13 pced1a LOC100490023 nat8.9 LOC100489681 nat8.7

Xla.Chr1L: nat8.5.L nat8.6.L LOC108697437 dctn1.L LOC121401558 GeneID:386623;adam13.L pced1a.L XB22166507.L LOC108719417 LOC108697487 LOC108719426

Xla.Chr1S: LOC108705748 nat8.6.S nat8.7.S LOC108704061 dctn1.S GeneID:373720;adam13.S LOC108706480 pced1a.S LOC108706478 cct7.S fbxo41.S

It appears that ADAM13 was lost in amniotes. The ADAM13 gene region in lower gnathostomes is quite variable so it's difficult to determine synteny outside of amphibia but we suspect the gene is present in most teleosts and sarcopterygian fish.

background to resolving adam13 v adam33 names

The protein ADAM13 (Alfandari et al., 1997 [1] is related to human ADAM33 but the sequences have diverged sufficiently that the two proteins cannot functionally replace each other.

Orthology (and thus accurate nomenclature) is being assessed by Xenbase and NCBI's ref seq and the HGNC.

ADAM13 is a cell surface metalloprotease that binds to its substrate via its cystein rich domain ([Gaultier et al., 2002][2]; [Smith et al., 2002][3]). ADAM13 binds and cleave fibronectin (Alfandari et al., 2001[4]), Cadherin-11 (McCusker et al., 2009[5]), PAPC (Cousin et al., 2011[6]) and ephrinB (Wei et al., 2011[7]).

ADAM13 also cleaves itself within its cystein rich domain (Gaultier et al., 2002[8]). This cleavage can be followed by a cleavage by gama-secretase that release the cytoplasmic domain. The ADAM13 cytoplasmic domain translocates into the nucleus where it regulates gene expression to promote cranial neural crest cell migration (Cousin et al., 2011[9]).

The cytoplasmic domain of ADAM13 interacts with multiple SH# containing proteins including PACSIN-2 which negatively regulates its proteolytic activity (Cousin et al., 2000 [10]).

Conservation across taxa According to Dom Alfandari, author a==fo several of the above mentioned papers, synteny and sequence conservation in Adam13 is good/conserved in Zebrafish, chicken and Monodelphis (gray opossum). Note that the cytoplasmic domain was lost in mammals [including mouse and human]. Thus, Xenopus Adam13 has orthologs in Zebrafish, Chicken and Monodelphis [which should really be called Adam13]. Mouse and Human Adam33 are distinct/different based on sequence, domains and synteny, and are NOT true orthologues of Xenopus Adam13.