BMC Cell Biology

, 7:18 | Cite as

A new standard nomenclature for proteins related to Apx and Shroom

  • Olivier Hagens
  • Andrea Ballabio
  • Vera Kalscheuer
  • Jean-Pierre Kraehenbuhl
  • M Vittoria Schiaffino
  • Peter Smith
  • Olivier Staub
  • Jeff Hildebrand
  • John B Wallingford
Open Access


Shroom is a recently-described regulator of cell shape changes in the developing nervous system. This protein is a member of a small family of related proteins that are defined by sequence similarity and in most cases by some link to the actin cytoskeleton. At present these proteins are named Shroom, APX, APXL, and KIAA1202. In light of the growing interest in this family of proteins, we propose here a new standard nomenclature.


Related Protein Anopheles Gambiae Standard Nomenclature Protein Family Member Arabic Number 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
In 1992, the primary structure of an a pical protein in X enopus (Apx) was described [1]. Since then, three related proteins have been characterized, namely the human proteins APXL (a pical p rotein X enopus-like) [2] and KIAA1202 [3] and mouse Shroom [4], named after the mouse mutant phenotype. We now know that the Apx protein of Xenopus is not in fact the orthologue of human APXL. Instead, the protein previously called human APXL2 is the likely homologue of frog Apx, while human APXL is the likely homologue of a Xenopus APXL. In this letter, we report a new standardized nomenclature to eliminate the confusing present naming situation for these proteins (Table 1).
Table 1

New nomenclature for Shroom-related proteins

GenBank Accession Number

Previous name

New name


X. laevis Apx



H. sapiens APXL2



H. sapiens APXL



M. musculus Apxl



M. musculus ShroomL



M. musculus ShroomS



H. sapiens Shroom



X. laevis Shroom-like



H. sapiens KIAA1202



H. sapiens SHAP-A



M. musculus KIAA1202



D. melanogaster Shroom



A. gambiae Shroom



A. mellifera Shroom



S. purpuratus Shroom


From global multiple alignments of genomic sequences, it is clear that these proteins are not simply encoded by homologous genes. There are in fact four different proteins in this family, showing similarity in their domains (Table 2), which include a PDZ and two A px/S hrm d omains (ASD1 and ASD2) and putative EVH1 and PDZ binding sites [4]. It should be noted however that Apx lacks the PDZ domain and the EVH1 binding site, APXL lacks a PDZ binding site and KIAA1202 does not contain an obvious ASD1 domain. Therefore, the ASD2 domain seems to be the common denominator among family members.
Table 2

Sequence identity matrix for the four different Shroom proteins which have been characterised experimentally.























a This table makes use of the new nomenclature presented in Table 1. To avoid evolution-based dissimilarity, the human homologues have been used in the analysis. b Percent sequence identity is given in the format global/PDZ/ASD1/ASD2; NA, not applicable. Global sequence identity is based on those residues aligning to hShroom1 residues 1 – 826. The alignments on which this matrix is based were created using ClustalW. They are available upon request.

Bioinformatics-based searches identified Shroom-related proteins in all chordates examined. In addition, insect genomes, including Drosophila melanogaster, Anopheles gambiae and Apis mellifera, encode a partially related protein containing an ASD2 domain (Table 1). Finally, BLAST searches of the deposited sequences from invertebrate genome projects identify what may be considered Shroom orthologues in both Ciona intestinalis (data not shown) and Strongylocentrotus purpuratus (Table 1). Based on the putative open reading frames and genomic organization, these predicted proteins contain, at least, the N-terminal PDZ domain and the C-terminally positioned ASD2 motif.

To clarify future studies, we propose a unifying nomenclature, emphasizing the relatedness of those proteins (Table 1). We feel that while the founding member is Apx, this name is undesirable as a root for naming this family because it requires that 'Xenopus' would appear in protein names from all species. Instead, we propose that the new nomenclature be based upon the name 'Shroom' as this is now the most thoroughly studied member of the family [4, 5, 6]. An Arabic number following 'Shroom' would distinguish between the different proteins. A lower-case letter would distinguish between different protein products encoded by the same locus generated by alternative mRNA processing. According to these rules, we suggest the re-naming presented in Table 1.

Several papers suggest that these related proteins play diverse and important roles in the development of the nervous system and other tissues [2, 3, 4, 5, 6, 7, 8]. Future studies will be required to show if sequence similarity among Shroom protein family members is mirrored by conservation of their cellular and molecular function.


  1. 1.
    Staub O, Verrey F, Kleyman TR, Benos DJ, Rossier BC, Kraehenbuhl JP: Primary structure of an apical protein from Xenopus laevis that participates in amiloride-sensitive sodium channel activity. J Cell Biol. 1992, 119 (6): 1497-1506. 10.1083/jcb.119.6.1497.CrossRefPubMedGoogle Scholar
  2. 2.
    Schiaffino MV, Bassi MT, Rugarli EI, Renieri A, Galli L, Ballabio A: Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region. Hum Mol Genet. 1995, 4 (3): 373-382.CrossRefPubMedGoogle Scholar
  3. 3.
    Hagens O, Dubos A, Abidi F, Barbi G, Van Zutven L, Hoeltzenbein M, Tommerup N, Moraine C, Fryns JP, Chelly J, van Bokhoven H, Gecz J, Dollfus H, Ropers HH, Schwartz CE, de Cassia Stocco Dos Santos R, Kalscheuer V, Hanauer A: Disruptions of the novel KIAA1202 gene are associated with X-linked mental retardation. Hum Genet. 2005, 1-13.Google Scholar
  4. 4.
    Hildebrand JD, Soriano P: Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice. Cell. 1999, 99 (5): 485-497. 10.1016/S0092-8674(00)81537-8.CrossRefPubMedGoogle Scholar
  5. 5.
    Haigo SL, Hildebrand JD, Harland RM, Wallingford JB: Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr Biol. 2003, 13 (24): 2125-2137. 10.1016/j.cub.2003.11.054.CrossRefPubMedGoogle Scholar
  6. 6.
    Hildebrand JD: Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J Cell Sci. 2005, 118: 5191-5203. 10.1242/jcs.02626.CrossRefPubMedGoogle Scholar
  7. 7.
    Prat AG, Holtzman EJ, Brown D, Cunningham CC, Reisin IL, Kleyman TR, McLaughlin M, Jackson GRJ, Lydon J, Cantiello HF: Renal epithelial protein (Apx) is an actin cytoskeleton-regulated Na+ channel. J Biol Chem. 1996, 271 (30): 18045-18053. 10.1074/jbc.271.30.17704.CrossRefPubMedGoogle Scholar
  8. 8.
    Zuckerman JB, Chen X, Jacobs JD, Hu B, Kleyman TR, Smith PR: Association of the epithelial sodium channel with Apx and alpha-spectrin in A6 renal epithelial cells. J Biol Chem. 1999, 274 (33): 23286-23295. 10.1074/jbc.274.33.23286.CrossRefPubMedGoogle Scholar

Copyright information

© Hagens et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Olivier Hagens
    • 1
  • Andrea Ballabio
    • 2
  • Vera Kalscheuer
    • 1
  • Jean-Pierre Kraehenbuhl
    • 3
  • M Vittoria Schiaffino
    • 4
  • Peter Smith
    • 5
  • Olivier Staub
    • 6
  • Jeff Hildebrand
    • 7
  • John B Wallingford
    • 8
  1. 1.Dept. of Human Molecular GeneticsMax Planck Institute for Molecular GeneticsBerlinGermany
  2. 2.Telethon Institute of Genetics and MedicineNaplesItaly
  3. 3.Swiss Institute for Experimental Cancer Research and the Institute of BiochemistryUniversity of LausanneLausanneSwitzerland
  4. 4.Dept. of BiotechnologySan Raffaele Scientific InstituteMilanItaly
  5. 5.Dept. of Physiology and BiophysicsUniversity of Alabama at BirminghamBirminghamUSA
  6. 6.Dept. of Pharmacology & ToxicologyUniversity of LausanneLausanneSwitzerland
  7. 7.Dept. of Biological SciencesUniversity of PittsburghPittsburghUSA
  8. 8.Dept. of Molecular Cell and Developmental Biology & Institute for Cellular and Molecular BiologyUniversity of TexasAustinUSA

Personalised recommendations