View source for Pannexin

{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Purinergic signalling}}
{{Pfam_box 
| Symbol = Pannexin
| Name = Pannexin 
| image = 
| width = 
| caption = 
| Pfam= 
| InterPro= IPR039099
| SMART= 
| Prosite =          
| SCOP =     
| TCDB =  1.A.25
| PDB= 
}}
{{infobox protein
| Name = pannexin 1
| caption = 
| image = 
| width = 
| HGNCid = 8599
| Symbol = PANX1
| AltSymbols = 
| EntrezGene = 24145
| OMIM = 608420
| RefSeq = NM_015368
| UniProt = Q96RD7
| PDB = 
| ECnumber = 
| Chromosome = 11
| Arm = q
| Band = 14
| LocusSupplementaryData = -q21
}}
{{infobox protein
| Name = pannexin 2
| caption = 
| image = 
| width = 
| HGNCid = 8600
| Symbol = PANX2
| AltSymbols = 
| EntrezGene = 56666
| OMIM = 608421
| RefSeq = NM_052839
| UniProt = Q96RD6
| PDB = 
| ECnumber = 
| Chromosome = 22
| Arm = q
| Band = 13 
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = pannexin 3
| caption = 
| image = 
| width = 
| HGNCid = 20573
| Symbol = PANX3
| AltSymbols = 
| EntrezGene = 116337
| OMIM = 608422
| RefSeq = NM_052959
| UniProt = Q96QZ0
| PDB = 
| ECnumber = 
| Chromosome = 11
| Arm = q
| Band = 24.2
| LocusSupplementaryData = 
}}
'''Pannexins''' (from Greek 'παν' — all, and from Latin 'nexus' — connection) are a family of vertebrate proteins identified by their homology to the invertebrate [[innexins]].<ref name="pmid10898987">{{cite journal | vauthors = Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S | title = A ubiquitous family of putative gap junction molecules | journal = Current Biology | volume = 10 | issue = 13 | pages = R473-4 | date = June 2000 | pmid = 10898987 | doi = 10.1016/S0960-9822(00)00576-5 | s2cid = 20001454 | doi-access = free | bibcode = 2000CBio...10.R473P }}</ref> While innexins are responsible for forming [[gap junctions]] in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane [[Ion channel|channels]] connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments (such as [[Adenosine triphosphate|ATP]] and [[sulforhodamine B]]).

Three pannexins have been described in [[Chordates]]: Panx1, Panx2 and Panx3.<ref name="pmid16989724">{{cite journal | vauthors = Litvin O, Tiunova A, Connell-Alberts Y, Panchin Y, Baranova A | title = What is hidden in the pannexin treasure trove: the sneak peek and the guesswork | journal = Journal of Cellular and Molecular Medicine | volume = 10 | issue = 3 | pages = 613–34 | year = 2006 | pmid = 16989724 | pmc = 3933146 | doi = 10.1111/j.1582-4934.2006.tb00424.x }}</ref>

== Function ==
Pannexins can form nonjunctional transmembrane channels for transport of molecules of less than 1000 Da. These hemichannels can be present in plasma, endoplasmic resticulum (ER) and Golgi membranes. They transport Ca<sup>2+</sup>, ATP, [[Inositol trisphosphate|inositol triphosphate]] and other small molecules and can form hemichannels with greater ease than connexin subunits.<ref>{{cite journal | vauthors = Shestopalov VI, Panchin Y | title = Pannexins and gap junction protein diversity | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 3 | pages = 376–94 | date = February 2008 | pmid = 17982731 | doi = 10.1007/s00018-007-7200-1 | s2cid = 23181471 | pmc = 11131650 }}</ref>  Pannexin 1 and pannexin 2 underlie channel function in neurons and contribute to ischemic brain damage.<ref>{{cite journal | vauthors = Bargiotas P, Krenz A, Hormuzdi SG, Ridder DA, Herb A, Barakat W, Penuela S, von Engelhardt J, Monyer H, Schwaninger M | title = Pannexins in ischemia-induced neurodegeneration | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 51 | pages = 20772–7 | date = December 2011 | pmid = 22147915 | pmc = 3251101 | doi = 10.1073/pnas.1018262108 | bibcode = 2011PNAS..10820772B | doi-access = free }}</ref>

Pannexin 1 has been shown to be involved in early stages of innate immunity through an interaction with the [[P2RX7|P2X7]] purinergic receptor.  Activation of the pannexin channel through binding of ATP to P2X7 receptor leads to the release of [[IL1B|interleukin-1β]].<ref name="pmid17036048">{{cite journal | vauthors = Pelegrin P, Surprenant A | title = Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor | journal = The EMBO Journal | volume = 25 | issue = 21 | pages = 5071–82 | date = November 2006 | pmid = 17036048 | pmc = 1630421 | doi = 10.1038/sj.emboj.7601378 }}</ref>

Hypothetical roles of pannexins in the nervous system include participating in sensory processing, synchronization between [[hippocampus]] and [[Cerebral cortex|cortex]], hippocampal plasticity, and propagation of calcium waves. Calcium waves are supported by glial cells, which help maintain and modulate neuronal [[metabolism]].  According to one of the hypotheses, pannexins also may participate in pathological reactions, including the neural damage after ischemia and subsequent cell death.<ref>{{cite journal | vauthors = Bargiotas P, Krenz A, Hormuzdi SG, Ridder DA, Herb A, Barakat W, Penuela S, von Engelhardt J, Monyer H, Schwaninger M | title = Pannexins in ischemia-induced neurodegeneration | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 51 | pages = 20772–7 | date = December 2011 | pmid = 22147915 | pmc = 3251101 | doi = 10.1073/pnas.1018262108 | bibcode = 2011PNAS..10820772B | doi-access = free }}</ref>

Pannexin 1 channels are pathways for release of ATP from cells.<ref name="pmid15304325">{{cite journal | vauthors = Bao L, Locovei S, Dahl G | title = Pannexin membrane channels are mechanosensitive conduits for ATP | journal = FEBS Letters | volume = 572 | issue = 1–3 | pages = 65–8 | date = August 2004 | pmid = 15304325 | doi = 10.1016/j.febslet.2004.07.009 | s2cid = 43459258 | doi-access =  | bibcode = 2004FEBSL.572...65B }}</ref>

== Relationship to connexins ==
Intercellular [[gap junction]]s in vertebrates, including humans, are formed by the [[connexin]] family of proteins.<ref name="pmid16801216">{{cite journal | vauthors = Dahl G, Locovei S | title = Pannexin: to gap or not to gap, is that a question? | journal = IUBMB Life | volume = 58 | issue = 7 | pages = 409–19 | date = July 2006 | pmid = 16801216 | doi = 10.1080/15216540600794526 | s2cid = 24038607 | doi-access = free }}</ref> Structurally, pannexins and connexins are very similar, consisting of 4 transmembrane domains, 2 extracellular and 1 intracellular loop, along with intracellular N- and C-terminal tails. Despite this shared topology, the protein families do not share enough sequence similarity to confidently infer common ancestry.

The N-terminal portion ({{Pfam|PF12534}}) of [[volume-regulated anion channel|VRAC]]-forming LRRC8 proteins like [[LRRC8A]] may also be related to pannexins.<ref>{{cite journal | vauthors = Abascal F, Zardoya R | title = LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell-cell communication | journal = BioEssays | volume = 34 | issue = 7 | pages = 551–60 | date = July 2012 | pmid = 22532330 | doi = 10.1002/bies.201100173 | hdl = 10261/124027 | s2cid = 24648128 | hdl-access = free }}</ref>

The structure of a ''[[Xenopus tropicalis]]'' (western clawed frog) pannexin ({{PDB|6VD7}}) has been solved. It forms a heptameric disc. The human version ({{PDB|6M02}}) is similar.<ref>{{cite journal | vauthors = Michalski K, Syrjanen JL, Henze E, Kumpf J, Furukawa H, Kawate T | title = The cryo-EM structure of a pannexin 1 reveals unique motifs for ion selection and inhibition | journal = eLife | volume = 9 | pages = e54670 | date = February 2020 | pmid = 32048993 | doi = 10.7554/eLife.54670 | doi-access = free | pmc = 7108861 }}</ref><ref>{{cite journal | vauthors = Qu R, Dong L, Zhang J, Yu X, Wang L, Zhu S | title = Cryo-EM structure of human heptameric Pannexin 1 channel | journal = Cell Research | date = March 2020 | pmid = 32203128 | doi = 10.1038/s41422-020-0298-5 | volume = 30 | issue = 5 | pmc = 7196123 | pages = 446–448}}</ref>

== Clinical significance ==
Truncating mutations in pannexin 1 have been shown to promote breast and colon cancer metastasis to the lungs by allowing cancer cells to survive mechanical stretch in the microcirculation through the release of ATP.<ref name="pmid26098574">{{cite journal | vauthors = Furlow PW, Zhang S, Soong TD, Halberg N, Goodarzi H, Mangrum C, Wu YG, Elemento O, Tavazoie SF | title = Mechanosensitive pannexin-1 channels mediate microvascular metastatic cell survival | journal = Nature Cell Biology | volume = 17 | issue = 7 | pages = 943–52 | date = July 2015 | pmid = 26098574 | pmc = 5310712 | doi = 10.1038/ncb3194 }}</ref>

Pannexins may be involved in the process of tumor development. Particularly, PANX2 expression levels predict post diagnosis survival for patients with glial tumors.

[[Probenecid]], a well-established drug for the treatment of [[gout]], allows for discrimination between channels formed by [[connexin]]s and pannexins. [[Probenecid]] does not affect channels formed by connexins, but it inhibits pannexin-1 channels.<ref name="pmid18596212">{{cite journal | vauthors = Silverman W, Locovei S, Dahl G | title = Probenecid, a gout remedy, inhibits pannexin 1 channels | journal = American Journal of Physiology. Cell Physiology | volume = 295 | issue = 3 | pages = C761-7 | date = September 2008 | pmid = 18596212 | pmc = 2544448 | doi = 10.1152/ajpcell.00227.2008 }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite book|author1=Andrew L Harris  |author2=Darren Locke  | title = Connexins, A Guide | publisher = Springer | year = 2009 | location = New York | pages = 574 | url = https://www.springer.com/978-1-934115-46-6  | isbn = 978-1-934115-46-6}}
{{refend}}

[[Category:Integral membrane proteins]]