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2  structures 75  species 0  interactions 259  sequences 9  architectures

Family: ASD2 (PF08687)

Summary: Apx/Shroom domain ASD2

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This is the Wikipedia entry entitled "Shroom protein family". More...

Shroom protein family Edit Wikipedia article

ASD1
Identifiers
Symbol ASD1
Pfam PF08688
InterPro IPR014800
ASD2
Identifiers
Symbol ASD2
Pfam PF08687
InterPro IPR014799

In molecular biology, the Shroom protein family is a small group of related proteins that are defined by sequence similarity and in most cases by some link to the actin cytoskeleton. The Shroom (Shrm) protein family is found only in animals. Proteins of this family are predicted to be utilised in multiple morphogenic and developmental processes across animal phyla to regulate cells shape or intracellular architecture in an actin and myosin-dependent manner.[1] While the founding member of the Shrm family is Shrm1 (formerly Apx), it appears that this protein is found only in Xenopus.[2] In mice and humans, the Shrm family of proteins consists of:

  • Shrm2 (formerly Apxl), a protein involved in the morphogenesis, maintenance, and/or function of vascular endothelial cells.
  • Shrm4, a regulator of cyto-skeletal architecture that may play an important role in vertebrate development. It is implicated in X-linked intellectual disability in humans.

This protein family is based on the conservation of a specific arrangement of an N-terminal PDZ domain, a centrally positioned sequence motif termed ASD1 (Apx/Shrm Domain 1) and a C-terminal motif termed ASD2.[1][2][3] Shrm2 and Shrm3 contain all three domains, while Shrm4 contains the PDZ and ASD2 domains, but lacks a discernible ASD1 element. To date, the ASD1 and ASD2 elements have only been found in Shrm-related proteins and do not appear in combination with other conserved domains. ASD1 is required for targeting actin, while ASD2 is capable of eliciting an actomyosin based constriction event.[1][2] ASD2 is the most highly conserved sequence element shared by Shrm1, Shrm2, Shrm3, and Shrm4. It possesses a well conserved series of leucine residues that exhibit spacing consistent with that of a leucine zipper motif.[1]

Shroom2 is both necessary and sufficient to govern the localization of pigment granules at the apical surface of epithelial cells. Shroom2 is a central regulator of RPE pigmentation. Despite their diverse biological roles, Shroom family proteins share a common activity. Since the locus encoding human SHROOM2 lies within the critical region for two distinct forms of ocular albinism, it is possible that SHROOM2 mutations may contribute to human visual system disorders.[4]

References[edit]

  1. ^ a b c d Dietz ML, Bernaciak TM, Vendetti F, Kielec JM, Hildebrand JD (July 2006). "Differential actin-dependent localization modulates the evolutionarily conserved activity of Shroom family proteins". J. Biol. Chem. 281 (29): 20542–54. doi:10.1074/jbc.M512463200. PMID 16684770. 
  2. ^ a b c Yoder M, Hildebrand JD (January 2007). "Shroom4 (Kiaa1202) is an actin-associated protein implicated in cytoskeletal organization". Cell Motil. Cytoskeleton 64 (1): 49–63. doi:10.1002/cm.20167. PMID 17009331. 
  3. ^ Hildebrand JD, Soriano P (November 1999). "Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice". Cell 99 (5): 485–97. doi:10.1016/S0092-8674(00)81537-8. PMID 10589677. 
  4. ^ Fairbank PD, Lee C, Ellis A, Hildebrand JD, Gross JM, Wallingford JB (October 2006). "Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium". Development 133 (20): 4109–18. doi:10.1242/dev.02563. PMID 16987870. 

This article incorporates text from the public domain Pfam and InterPro IPR014799

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Apx/Shroom domain ASD2 Provide feedback

This region is found in the actin binding protein Shroom which mediates apical contriction in epithelial cells and is required for neural tube closure.

Literature references

  1. Hildebrand JD; , J Cell Sci. 2005;118:5191-5203.: Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. PUBMED:16249236 EPMC:16249236

  2. Haigo SL, Hildebrand JD, Harland RM, Wallingford JB; , Curr Biol. 2003;13:2125-2137.: Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. PUBMED:14680628 EPMC:14680628

  3. Hildebrand JD, Soriano P; , Cell. 1999;99:485-497.: Shroom, a PDZ domain-containing actin-binding protein, is required for neural tube morphogenesis in mice. PUBMED:10589677 EPMC:10589677


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR014799

Cell shape changes require the coordination of actin and microtubule cytoskeletons. The Shroom family is a small group of related proteins that are defined by sequence similarity and in most cases by some link to the actin cytoskeleton. The Shroom (Shrm) protein family is found only in animals. Proteins of this family are predicted to be utilised in multiple morphogenic and developmental processes across animal phyla to regulate cells shape or intracellular architecture in an actin and myosin-dependent manner [PUBMED:16684770]. While the founding member of the Shrm family is Shrm1 (formerly Apx), it appears that this protein is found only in Xenopus [PUBMED:17009331]. In mice and humans, the Shrm family of proteins consists of:

  • Shrm2 (formerly Apxl), a protein involved in the morphogenesis, maintenance, and/or function of vascular endothelial cells.
  • Shrm3 (formerly Shroom), a protein necessary for neural tube closure in vertebrate development as deficiency in Shrm results in spina bifida. Shrm3 is also conserved in some invertebrates, as orthologues can be found in sea urchins.
  • Shrm4, a regulator of cyto-skeletal architecture that may play an important role in vertebrate development. It is implicated in X-linked mental retardation in humans.

This protein family is based on the conservation of a specific arrangement of an N-terminal PDZ domain, a centrally positioned sequence motif termed ASD1 (Apx/Shrm Domain 1) and a C-terminal motif termed ASD2 [PUBMED:16684770, PUBMED:17009331, PUBMED:10589677]. Shrm2 and Shrm3 contain all three domains, while Shrm4 contains the PDZ and ASD2 domains, but lacks a discernible ASD1 element. To date, the ASD1 and ASD2 elements have only been found in Shrm-related proteins and do not appear in combination with other conserved domains. ASD1 is required for targeting actin, while ASD2 is capable of eliciting an actomyosin based constriction event [PUBMED:16684770, PUBMED:17009331]. ASD2 is the most highly conserved sequence element shared by Shrm1, Shrm2, Shrm3, and Shrm4. It possesses a well conserved series of leucine residues that exhibit spacing consistent with that of a leucine zipper motif [PUBMED:16684770].

Shroom2 is both necessary and sufficient to govern the localization of pigment granules at the apical surface of epithelial cells. Shroom2 is a central regulator of RPE pigmentation. Despite their diverse biological roles, Shroom family proteins share a common activity. Since the locus encoding human SHROOM2 lies within the critical region for two distinct forms of ocular albinism, it is possible that SHROOM2 mutations may contribute to human visual system disorders [PUBMED:16987870].

Gene Ontology

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Domain organisation

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Alignments

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  Seed
(14)
Full
(259)
Representative proteomes NCBI
(229)
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(0)
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(20)
RP35
(30)
RP55
(74)
RP75
(149)
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Format an alignment

  Seed
(14)
Full
(259)
Representative proteomes NCBI
(229)
Meta
(0)
RP15
(20)
RP35
(30)
RP55
(74)
RP75
(149)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(14)
Full
(259)
Representative proteomes NCBI
(229)
Meta
(0)
RP15
(20)
RP35
(30)
RP55
(74)
RP75
(149)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Seed source: manual
Previous IDs: none
Type: Family
Author: Mistry J, Hildebrand JD
Number in seed: 14
Number in full: 259
Average length of the domain: 247.60 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 24.19 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.6 23.6
Noise cut-off 23.4 23.4
Model length: 264
Family (HMM) version: 6
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the ASD2 domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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