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24  structures 308  species 0  interactions 3827  sequences 43  architectures

Family: Innexin (PF00876)

Summary: Innexin

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Innexin Edit Wikipedia article

Innexin
Identifiers
Symbol Innexin
Pfam PF00876
InterPro IPR000990
TCDB 1.A.25
OPM superfamily 215
OPM protein 5h1r

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.

Discovery

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).[1] 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).[2][3] However, increasing evidence suggests that pannexins do not form gap junctions unless overexpressed in tissue and thus, differ functionally from innexins.[4]

Structure

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.[5] 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.[6]

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.[7][8]

Function

Pannexins can form nonjunctional transmembrane “hemichannels” 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.[9] Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes.[10] Pannexin 1 and pannexin 2 underlie channel function in neurons and contribute to ischemic brain damage.[11]

In addition to making gap junctions, innexins also form non-junctional membrane channels with properties similar to those of pannexons.[12] 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.[13]

Transport reaction

The transport reactions catalyzed by innexin gap junctions is:

Small molecules (cell 1 cytoplasm) ⇌ small molecules (cell 2 cytoplasm)

Or for hemichannels:

Small molecules (cell cytoplasm) ⇌ small molecules (out)

Examples

See also

References

  1. ^ 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): 181–184. doi:10.1038/34426. PMID 9428764. 
  2. ^ 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): R473–4. doi:10.1016/S0960-9822(00)00576-5. PMID 10898987. 
  3. ^ 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): 2475–2476. doi:10.1046/j.1460-9568.2002.02423.x. PMID 12492443. 
  4. ^ 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
  5. ^ Bao, L.; Samuels, S.; Locovei, S.; MacAgno, E.; Muller, K.; Dahl, G. (2007). "Innexins Form Two Types of Channels". FEBS Letters. 581 (29): 5703–5708. doi:10.1016/j.febslet.2007.11.030. PMC 2489203Freely accessible. PMID 18035059. 
  6. ^ 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): 24420–24431. doi:10.1074/jbc.M110.115444. ISSN 1083-351X. PMC 2915678Freely accessible. PMID 20516070. 
  7. ^ Turnbull M, Webb B (2002). "Perspectives on polydnavirus origins and evolution". Adv. Virus Res. 58: 203–254. doi:10.1016/S0065-3527(02)58006-4. PMID 12205780. 
  8. ^ Kroemer JA, Webb BA (2004). "Polydnavirus genes and genomes: emerging gene families and new insights into polydnavirus replication". Annu Rev Entomol. 49 (1): 431–456. doi:10.1146/annurev.ento.49.072103.120132. PMID 14651471. 
  9. ^ Shestopalov, V. I.; Panchin, Y. (2008-02-01). "Pannexins and gap junction protein diversity". Cellular and molecular life sciences: CMLS. 65 (3): 376–394. doi:10.1007/s00018-007-7200-1. ISSN 1420-682X. PMID 17982731. 
  10. ^ Limaye, S. R.; Mahmood, M. A. (1987-10-01). "Retinal microangiopathy in pigmented paravenous chorioretinal atrophy". The British Journal of Ophthalmology. 71 (10): 757–761. doi:10.1136/bjo.71.10.757. ISSN 0007-1161. PMC 1041301Freely accessible. PMID 3676145. 
  11. ^ 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): 20772–20777. doi:10.1073/pnas.1018262108. ISSN 1091-6490. PMC 3251101Freely accessible. PMID 22147915. 
  12. ^ 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): 5703–5708. doi:10.1016/j.febslet.2007.11.030. ISSN 0014-5793. PMC 2489203Freely accessible. PMID 18035059. 
  13. ^ 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): 24–37. doi:10.1002/arch.21328. ISSN 1520-6327. PMID 27030553. 

Further reading

External links

This article incorporates text from the public domain Pfam and InterPro IPR000990

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.

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.

Innexin Provide feedback

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 [1]. This family has been named the Innexins [2].

Literature references

  1. Phelan P, Stebbings LA, Baines RA, Bacon JP, Davies JA, Ford C; , Nature 1998;391:181-184.: Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes. PUBMED:9428764 EPMC:9428764

  2. 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

  3. Phelan P,Starich TA , Bioessays 2001;23:388-396.: Innexins get into the gap. PUBMED:11340620 EPMC:11340620


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000990

The pannexin family combines invertebrate gap junction proteins and their vertebrate homologues. These proteins have been named innexins [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.

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan Transporter (CL0375), which has the following description:

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 12 members:

Amastin Claudin_2 Claudin_3 Clc-like Connexin Fig1 GSG-1 Innexin L_HMGIC_fpl Pannexin_like PMP22_Claudin SUR7

Alignments

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(221)
Full
(3827)
Representative proteomes UniProt
(5860)
NCBI
(5018)
Meta
(1)
RP15
(530)
RP35
(788)
RP55
(1089)
RP75
(1202)
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  Seed
(221)
Full
(3827)
Representative proteomes UniProt
(5860)
NCBI
(5018)
Meta
(1)
RP15
(530)
RP35
(788)
RP55
(1089)
RP75
(1202)
Alignment:
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  Seed
(221)
Full
(3827)
Representative proteomes UniProt
(5860)
NCBI
(5018)
Meta
(1)
RP15
(530)
RP35
(788)
RP55
(1089)
RP75
(1202)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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

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.

Curation View help on the curation process

Seed source: Pfam-B_779 (release 3.0)
Previous IDs: Ogre;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 221
Number in full: 3827
Average length of the domain: 263.10 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 74.38 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.3 22.3
Trusted cut-off 22.3 22.3
Noise cut-off 22.2 22.2
Model length: 351
Family (HMM) version: 18
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 Innexin domain has been found. There are 24 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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