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Innexin Edit Wikipedia article
Innexins are transmembrane proteins that form gap junctions in invertebrates. Gap junctions are composed of membrane proteins that form a channel permeable to ions and small molecules connecting the cytoplasm of adjacent cells. Although gap junctions provide similar functions in all multicellular organisms, it was not known what proteins invertebrates used for this purpose until the late 1990s. While the connexin family of gap junction proteins was well-characterized in vertebrates, no homologues were found in non-chordates.
Gap junction proteins with no sequence homology to connexins were initially identified in fruit flies. It was suggested that these proteins are specific invertebrate gap junctions, and they were thus named "innexins" (invertebrate analog of connexins). They were later identified in diverse invertebrates. Invertebrate genomes may contain more than a dozen innexin genes. Once the human genome was sequenced, innexin homologues were identified in humans and then in other vertebrates, indicating their ubiquitous distribution in the animal kingdom. These homologues were called "pannexins" (from the Greek pan - all, throughout, and Latin nexus - connection, bond). However, increasing evidence suggests that pannexins do not form gap junctions unless overexpressed in tissue and thus, differ functionally from innexins.
Innexins have four transmembrane segments (TMSs) and, like the vertebrate connexin gap junction protein, six innexin subunits together form a channel (an "innexon") in the plasma membrane of the cell. Two innexons in apposed plasma membranes can form a gap junction. Structurally, pannexins are similar to connexins. Both types of protein consist of a cytoplasmic N-terminal domain, followed by four (TMSs) that delimit one cytoplasmic and two extracellular loops; the C- terminal domain is cytoplasmic. In addition, pannexin1 and pannexin2 channels show quaternary similarities to connexons, but different oligomerization numbers.
Vinnexins, viral homologues of innexins, were identified in polydnaviruses that occur in obligate symbiotic associations with parasitoid wasps. It was suggested that vinnexins may function to alter gap junction proteins in infected host cells, possibly modifying cell-cell communication during encapsulation responses in parasitized insects.
Pannexins can form nonjunctional transmembrane â€œhemichannelsâ€ for transport of molecules of less than 1000 Da, or intercellular gap junctions. These hemichannels can be present in plasma, ER and Golgi membranes. They transport Ca2+, ATP, inositol triphosphate and other small molecules and can form hemichannels with greater ease than connexin subunits. Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes. Pannexin 1 and pannexin 2 underlie channel function in neurons and contribute to ischemic brain damage.
In addition to making gap junctions, innexins also form non-junctional membrane channels with properties similar to those of pannexons. N-terminal- elongated innexins can act as a plug to manipulate hemichannel closure and provide a mechanism connecting the effect of hemichannel closure directly to apoptotic signal transduction from the intracellular to the extracellular compartment.
The transport reactions catalyzed by innexin gap junctions is:
- Small molecules (cell 1 cytoplasm) â‡Œ small molecules (cell 2 cytoplasm)
Or for hemichannels:
- Small molecules (cell cytoplasm) â‡Œ small molecules (out)
- Caenorhabditis elegans
- Drosophila melanogaster
- Inx4 (zero population growth, zpg)
- Hirudo medicinalis
- Phelan P, Stebbings LA, Baines RA, Bacon JP, Davies JA, Ford C (1998). "Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes". Nature. 391 (6663): 181â€“184. Bibcode:1998Natur.391..181P. doi:10.1038/34426. PMID 9428764.
- Lukyanov S, Usman N, Panchin Y, Kelmanson I, Matz M, Lukyanov K (2000). "A ubiquitous family of putative gap junction molecules". Curr. Biol. 10 (13): R473â€“4. doi:10.1016/S0960-9822(00)00576-5. PMID 10898987.
- Matz MV, Lukyanov SA, Kelmanson IV, Shagin DA, Usman N, Panchin YV (2002). "Altering electrical connections in the nervous system of the pteropod mollusc Clione limacina by neuronal injections of gap junction mRNA". Eur. J. Neurosci. 16 (12): 2475â€“2476. doi:10.1046/j.1460-9568.2002.02423.x. PMID 12492443.
- Dahl G. & Harris A. 2009. Pannexins or Connexins? Chapter 12. In: A. Harris, D. Locke (eds.), Connexins: A Guide doi:10.1007/978-1-59745-489-6_12
- Bao, L.; Samuels, S.; Locovei, S.; MacAgno, E.; Muller, K.; Dahl, G. (2007). "Innexins Form Two Types of Channels". FEBS Letters. 581 (29): 5703â€“5708. doi:10.1016/j.febslet.2007.11.030. PMC 2489203. PMID 18035059.
- Ambrosi, Cinzia; Gassmann, Oliver; Pranskevich, Jennifer N.; Boassa, Daniela; Smock, Amy; Wang, Junjie; Dahl, Gerhard; Steinem, Claudia; Sosinsky, Gina E. (2010-08-06). "Pannexin1 and Pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other". The Journal of Biological Chemistry. 285 (32): 24420â€“24431. doi:10.1074/jbc.M110.115444. ISSN 1083-351X. PMC 2915678. PMID 20516070.
- Turnbull M, Webb B (2002). "Perspectives on polydnavirus origins and evolution". Adv. Virus Res. Advances in Virus Research. 58: 203â€“254. doi:10.1016/S0065-3527(02)58006-4. ISBN 9780120398584. PMID 12205780.
- Kroemer JA, Webb BA (2004). "Polydnavirus genes and genomes: emerging gene families and new insights into polydnavirus replication". Annu Rev Entomol. 49 (1): 431â€“456. doi:10.1146/annurev.ento.49.072103.120132. PMID 14651471.
- Shestopalov, V. I.; Panchin, Y. (2008-02-01). "Pannexins and gap junction protein diversity". Cellular and Molecular Life Sciences. 65 (3): 376â€“394. doi:10.1007/s00018-007-7200-1. ISSN 1420-682X. PMID 17982731.
- Limaye, S. R.; Mahmood, M. A. (1987-10-01). "Retinal microangiopathy in pigmented paravenous chorioretinal atrophy". The British Journal of Ophthalmology. 71 (10): 757â€“761. doi:10.1136/bjo.71.10.757. ISSN 0007-1161. PMC 1041301. PMID 3676145.
- Bargiotas, Panagiotis; Krenz, Antje; Hormuzdi, Sheriar G.; Ridder, Dirk A.; Herb, Anne; Barakat, Waleed; Penuela, Silvia; von Engelhardt, Jakob; Monyer, Hannah (2011-12-20). "Pannexins in ischemia-induced neurodegeneration". Proceedings of the National Academy of Sciences of the United States of America. 108 (51): 20772â€“20777. Bibcode:2011PNAS..10820772B. doi:10.1073/pnas.1018262108. ISSN 1091-6490. PMC 3251101. PMID 22147915.
- Bao, Li; Samuels, Stuart; Locovei, Silviu; Macagno, Eduardo R.; Muller, Kenneth J.; Dahl, Gerhard (2007-12-11). "Innexins form two types of channels". FEBS Letters. 581 (29): 5703â€“5708. doi:10.1016/j.febslet.2007.11.030. ISSN 0014-5793. PMC 2489203. PMID 18035059.
- Chen, Ya-Bin; Xiao, Wei; Li, Ming; Zhang, Yan; Yang, Yang; Hu, Jian-Sheng; Luo, Kai-Jun (2016-05-01). "N-TERMINALLY ELONGATED SpliInx2 AND SpliInx3 REDUCE BACULOVIRUS-TRIGGERED APOPTOSIS VIA HEMICHANNEL CLOSURE". Archives of Insect Biochemistry and Physiology. 92 (1): 24â€“37. doi:10.1002/arch.21328. ISSN 1520-6327. PMID 27030553.
- Phelan P, Bacon J, Davies J, Stebbings L, Todman M, Avery L, Baines R, Barnes T, Ford C, Hekimi S, Lee R, Shaw J, Starich T, Curtin K, Sun Y, Wyman R (1998). "Innexins: a family of invertebrate gap-junction proteins". Trends Genet. 14 (9): 348â€“9. doi:10.1016/S0168-9525(98)01547-9. PMC 4442478. PMID 9769729.
- Phelan P, Stebbings L, Baines R, Bacon J, Davies J, Ford C (1998). "Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes". Nature. 391 (6663): 181â€“4. Bibcode:1998Natur.391..181P. doi:10.1038/34426. PMID 9428764.
- Dykes I, Macagno E (2006). "Molecular characterization and embryonic expression of innexins in the leech Hirudo medicinalis". Dev Genes Evol. 216 (4): 185â€“97. doi:10.1007/s00427-005-0048-1. PMID 16440200.
As of this edit, this article uses content from "1.A.25 The Gap Junction-forming Innexin (Innexin) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.
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This family includes the Drosophila proteins Ogre and shaking-B, and the C. elegans proteins Unc-7 and Unc-9. Members of this family are integral membrane proteins which are involved in the formation of gap junctions . This family has been named the Innexins .
Phelan P, Bacon JP, Davies JA, Stebbings LA, Todman MG, Avery L, Baines RA, Barnes TM, Ford C, Hekimi S, Lee R, Shaw JE, Starich TA, Curtin KD, Sun Y, Wyman RJ; , Trends Genet 1998;14:348-349.: Innexins: a family of invertebrate gap-junction proteins. PUBMED:9769729 EPMC:9769729
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000990
This entry includes pannexins from vertebrates and innexins from invertebrate [ PUBMED:9769729 ]. Gap junctions are composed of membrane proteins, which form a channel permeable for ions and small molecules connecting cytoplasm of adjacent cells. Although gap junctions provide similar functions in all multicellular organisms, until recently it was believed that vertebrates and invertebrates use unrelated proteins for this purpose. While the connexins family of gap junction proteins is well- characterised in vertebrates, no homologues have been found in invertebrates. In turn, gap junction molecules with no sequence homology to connexins have been identified in insects and nematodes. It has been suggested that these proteins are specific invertebrate gap junctions, and they were thus named innexins (invertebrate analog of connexins) [ PUBMED:9428764 ]. As innexin homologues were recently identified in other taxonomic groups including vertebrates, indicating their ubiquitous distribution in the animal kingdom, they were called pannexins (from the Latin pan-all, throughout, and nexus-connection, bond) [ PUBMED:10898987 , PUBMED:12492443 , PUBMED:5028292 ].
Genomes of vertebrates carry probably a conserved set of 3 pannexin paralogs (PANX1, PANX2 and PANX3). Invertebrate genomes may contain more than a dozen pannexin (innexin) genes. Vinnexins, viral homologues of pannexins/innexins, were identified in Polydnaviruses that occur in obligate symbiotic associations with parasitoid wasps. It was suggested that virally encoded vinnexin proteins may function to alter gap junction proteins in infected host cells, possibly modifying cell-cell communication during encapsulation responses in parasitized insects [ PUBMED:12205780 , PUBMED:14651471 ]. Structurally pannexins are simillar to connexins. Both types of protein consist of a cytoplasmic N-terminal domain, followed by four transmembrane segments that delimit two extracellular and one cytoplasmic loops; the C- terminal domain is cytoplasmic.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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The members of this superfamily are probably all transporter protein domains. All families normally carry four tansmembrane regions, which in many instances associate into hexameric structures. They are frequently involved in gap-junction formation between cells or in forming pores linking the cytosol with the extracellulare space 1,2]. The clan includes members of the TCDB superfamilies 1.A.24 and 1.A.25.
The clan contains the following 13 members:Amastin Atthog Claudin_2 Claudin_3 Clc-like Connexin Fig1 GSG-1 Innexin L_HMGIC_fpl Pannexin_like PMP22_Claudin SUR7
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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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.
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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
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_779 (release 3.0)|
|Number in seed:||177|
|Number in full:||4255|
|Average length of the domain:||265.40 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||71.69 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||20|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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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 Innexin domain has been found. There are 167 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 sequence.
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