Connexin 43 (gap junction α-1 protein), CX43 encoded by the GJA1 gene (transports ATP, ADP and AMP better than CX32 does; Goldberg et al., 2002). Hemichannels mediate efflux of glutathione, glutamate and other amino acids as well as ATP (Stridh et al., 2008; Kang et al., 2008). CX43 has a half life of ~3 h due to ubiquitination and lysosomal and proteasomal degradation (Leithe and Rivedal, 2007). Cx43 and Cx46 regulate each other's expression and turnover in a reciprocal manner in addition to their conventional roles as gap junction proteins in lens cells (Banerjee et al., 2011). A mutant form of Connexin 43 causes Oculodentodigital dysplasia (Gabriel et al., 2011).  Suppressing the function of Cx43 promotes expression of wound healing-associated genes and hibitits scarring (Tarzemany et al. 2015).  Channel conductance and size selectivity are largely determined by pore diameter, whereas charge selectivity results from the amino-terminal domains; transitions between fully open and (multiple) closed states involves global changes in structure of the pore-forming domains (Ek Vitorín et al. 2016). The human Cx43 orthologue is almost identical to the rat protein.  It may mediate resistance against the parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP⁺) which induces apoptosis in neuroblastoma cells by modulating mitochondrial apoptosis (Kim et al. 2016).  Dopamine neurons may be the target of MPP⁺ and play a role in Parkinson's disease. In humans, Cx43 plays roles in the development of the central nervous system and in the progression of glioma (Wang et al. 2017).  It interacts with and is regulated by many proteins including NOV (CCN3, IGFBP9; P48745) (Giepmans 2006). Cx43 plays roles in intercellular communication mediated by extracellular vesicles, tunnelling nanotubes and gap junctions (Ribeiro-Rodrigues et al. 2017). Phosphorylation of Cx43 leads to astrocytic coupling and apoptosis, and ultimately, to vascular regeneration in retinal ischemia. Paxillin (Pxn; 591 aas; P49023), a cytoskeletal protein involved in focal adhesion, leads to changes in connexin 43 by direct protein-protein binding, thereby influencing osteocyte gap junction elongation (Zhang et al. 2018). Regulation of Cx43 abundance involves transcriptional/post-transcriptional and translational/post-translational mechanisms that are modulated by an interplay between TGF-beta isoforms and PGE2, IL-1beta, TNF-alpha and IFN-gamma (Cheng et al. 2018). In the developing fetal human kidney, cytoplasmic expression of Cx36 was localized to nephrons in different developmental stages, glomerular vessels and collecting ducts, and of Cx43 was localized to the endothelium of glomerular and peritubular vessels, as well as to the epithelium of the proximal tubules (Ráduly et al. 2019). Mutations in the gap junction protein α1 (GPA1) gene cause oculodentodigital dysplasia (Pace et al. 2019). Expression of connexin 43 is elevated in atypical fibroxanthoma cells (Fernandez-Flores et al. 2020). Astrocytic connexin43 channels are candidate targets in epilepsy treatment (Walrave et al. 2020). Cx43 plays roles in physiological functions such as regulating cell growth, differentiation, and maintaining tissue homeostasis (Sha et al. 2020). Amyloid-beta (TC# 1.C.50) regulates connexin 43 trafficking in cultured primary astrocytes (Maulik et al. 2020). Gap junction protein Cx43 plays a role in regulating cellular function and paracrine effects of smooth muscle progenitor cells (Tien (田婷怡) et al. 2021). A serine residues in the connexin43 carboxyl tail is important for B-cell antigen receptor-mediated spreading of B-lymphocytes (Pournia et al. 2020). Connexin 43 plays an antagonistic role in the development of primary bone tumors as a tumor suppressor and also as a tumor promoter (Talbot et al. 2020). Retinal astrocytes abundantly express Cx43 that forms gap junction (GJ) channels and unopposed hemichannels, and Cx43 is upregulated in retinal injuries. Astrocytic Cx43 plays a role in retinal ganglion cell (RGC) loss associated with injury (Toychiev et al. 2021). Screens for inhibitors of Cx43 hemichannel function have revealed several candidates (Soleilhac et al. 2021). The dodecameric channel is formed by the end-to-end docking of two hexameric connexons, each comprised of 24 transmembrane alpha-helices (Cheng et al. 2019). Cx43 appears to be involved in the tumorigenesis of most pituitary adenomas and have a potential therapeutic value for pituitary tumor therapy (Nunes et al. 2022). Yang et al. 2023 provided an updated understanding of connexin hemichannels and pannexin channels in response to multiple extrinsic stressors and how these activated channels and their permeable messengers participate in toxicological pathways and processes, including inflammation, oxidative damage and intracellular calcium imbalance (Yang et al. 2023). Remodeled connexin 43 hemichannels alter cardiac excitability and promote arrhythmias (Lillo et al. 2023). Insulin docking within the open hemichannel of connexin 43 may reduce risk of amyotrophic lateral sclerosis (Lehrer and Rheinstein 2023).

Animals

CX43 of Rattus norvegicus

Connexin31, Cx31 of 270 aas and 4 TMSs.  Also called the gap junction β-3 protein. Mutation Thr202Asn in TMS4 gives rise to erythrokeratodermia (Sugiura et al. 2015).

Cx31 of Homo sapiens

Gap junction α-1 protein, GJα-1, Cx43, shf, sof, of 281 aas and 4 TMSs.  Can function both as a gap junction and a hemichannel and plays critical diverse roles in zebrafish bone growth (Misu et al. 2016).

Cx43 of Danio rerio (Zebrafish) (Brachydanio rerio)

Connexin 29 (Cx29, Gjc3, Gje1) of 269 aas and 4 TMSs.  The Cx29E269D mutant has a dominant negative effect on the formation and function of gap junctions, explaining the role Cx29 in the development of hearing loss (Hong et al. 2010).  Direct axon-to-myelin linkage by abundant K_V1 (TC# 1.A.1.2.10 and 12)/Cx29 channel interactions in rodent axons supports the idea of an electrically active role for myelin in increasing both the saltatory conduction velocity and the maximal propagation frequency in mammalian myelinated axons (Rash et al. 2016).

Cx29 of Mus musculus

Connexin36, connexin delta2, Cxδ2, GJD2, Cx36 of 321 aas and 4 TMSs. In the developing fetal kidney, cytoplasmic expression of Cx36 is localized to nephrons in different developmental stages, glomerular vessels and collecting ducts. Cx43 is localized to the endothelium of glomerular and peritubular vessels, as well as to the epithelium of the proximal tubules (Ráduly et al. 2019). A reciprocal relationship between Cx36 and seizure-associated neuronal hyperactivityhas been obseerved; thus, Cx36 deficiency contributes to region-specific susceptibility to neuronal hyperactivity, while neuronal hyperactivity-induced downregulation of Cx36 may increase the risk of future epileptic events (Brunal et al. 2020). Cx36 is responsible for signal transmission in electrical synapses by forming interneuronal gap junctions. Lee et al. 2023 determined cryo-electron microscopy structures of Cx36 GJC at 2.2-3.6 Å resolutions, revealing a dynamic equilibrium between its closed and open states. In the closed state, channel pores are obstructed by lipids, while N-terminal TMSs are excluded from the pore. In the open state with pore-lining N-terminal TMSs, the pore is more acidic than those in Cx26 and Cx46/50 GJCs, explaining its strong cation selectivity. The conformational change during channel opening also includes the alpha-to-pi-helix transition of the first transmembrane helix, which weakens the protomer-protomer interaction (Lee et al. 2023).

Cx36 of Homo sapiens

Gap junction protein B4, GJB4, or Cx30.3 of 266 aas and 4 TMSs. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore in these dodecameric channels. Mutation can cause a familial form of hypertrophic cardiomyopathy (HCM) and therefore could be a target for the treatment of cardiac hypertrophy and dysfunction (Okamoto et al. 2020). Cx30 and Cx26 hemichannels display similar permeabilities to ATP, but Cx26 gap junctions are six times more permeable than their hemichannels and four times more permeable than Cx30 gap junctions (Xu and Nicholson 2023).

GJB4 of Homo sapiens

Gap junction protein alpha 5, GJA5 or CxA5, of 358 aas and 4 TMSs. One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. GAJ5 is enriched for the function of ion transmembrane transport regulation and is a key atrial fibrillation (AF)-valvular heart disease (VHD) protein (Zhao et al. 2021).

Connexin-43, Cx43, or Gap Junction α-1 protein, GJA1, of 382 aas and 4 TMSs in a 2 + 2 TMS arrangement.  Extracellular vesicles enriched in connexin 43 promote a senescent phenotype in bone and synovial cells, contributing to osteoarthritis progression (Varela-Eirín et al. 2022). It is 98% identical to the rat ortholog (TC# 1.A.24.1.1).  Cx43 expression is highly sensitive to oxidative distress, leading to reduced expression (Wahl et al. 2022). This effect can be efficiently prevented by the glutathione peroxidase mimetic ebselen. Cx43 expression is tightly regulated by miR-1, which is activated by tachypacing-induced oxidative distress. In light of the high arrhythmogenic potential of altered Cx43 expression, miR-1 may be a target for pharmacological interventions to prevent the maladaptive remodeling processes during chronic distress in the heart (Wahl et al. 2022). Cx43 hemichannels can reversibly transport NAD⁺ and cyclic ADP-ribose, the latter which acts on cytoplasmic ryanodine receptors (RyRs) (Astigiano et al. 2022). Connexin 43 hemichannels regulate mitochondrial ATP generation, mobilization, and mitochondrial homeostasis against oxidative stress (Zhang et al. 2022). Cx43 and Cx32 catalyze ATP release from cells (Tovar et al. 2023). Jiang et al. 2023 have summarized the association between Cx43 and neuroinflammation, the cornerstones linking inflammation and depression, and Cx43 abnormalities in depression. The orally delivered Connexin43 hemichannel blocker, tonabersat, inhibits vascular breakdown and inflammasome activation in a mouse model of diabetic retinopathy suggesting that tonabersat may be a safe and effective treatment for DR (Mugisho et al. 2023). Conformational changes in the human Cx43/GJA1 gap junction channel have been visualized using cryo-EM (Lee et al. 2023). Simvastatin is an adjuvant in doxorubicin anticancer therapy. Its antioxidant and antiapoptotic activityies showed that Simvastatin interferes with expression and cellular localization of Cx43 that is widely involved in cardioprotection (Pecoraro et al. 2023). CX43 down-regulation promotes cell aggressiveness and 5-fluorouracil-resistance by attenuating cell stiffness in colorectal carcinoma (Han et al. 2023). The structure of a human Cx43 GJC has been solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. A previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 are stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement (Qi et al. 2023). Opening of Cx43-formed hemichannels mediates the Ca²⁺ signaling associated with endothelial cell migration (Espinoza and Figueroa 2023). The roles of Cx43 in disease development from the perspective of subcellular localization have been summarized (Xiong et al. 2023). Opening of Cx43-formed hemichannels mediates the Ca²⁺ signaling associated with endothelial cell migration (Espinoza and Figueroa 2023).   Targeting Cx43 reduces the severity of pressure ulcer progression (Kwek et al. 2023).  Multiple sclerosis (MS) is a neurodegenerative disease marked by chronic neuroinflammation thought to be mediated by the inflammasome pathway. Connexin 43 (Cx43) hemichannels contribute to the activation of the inflammasome through the release of adenosine triphosphate (ATP) inflammasome activation signals.  Tonabersat significantly reduces disease progression in an experimental mouse model of multiple sclerosis (Kwakowsky et al. 2023).  The E3 ubiquitin ligase ITCH negatively regulates intercellular communication via gap junctions by targeting connexin43 for lysosomal degradation (Totland et al. 2024). Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage (Gómez et al. 2024).  Differential regulation of Cx43 hemichannels and gap junction channels by RhoA GTPase and the actin cytoskeleton has been observed (Jara et al. 2024).

Cx43 of Homo sapiens

Connexin 32 (gap junction β1-protein), CX32 (transports adenosine better than CX43 does; Goldberg et al., 2002).  The carboxyl tail regulates gap junction assembly (Katoch et al. 2015).  The modeled channel pore-facing regions of TMSs 1 and 2 were highly sensitive to tryptophan substitution while lipid-facing regions of TMSs 3 and 4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also sensitive.  Interactions important for voltage gating occurred mainly in the mid-region of the channel in TMS 1. TMS 1 of Cx43 was scanned revealing similar but not identical sensitivities (Brennan et al. 2015). Single point mutations in Cx32, which cause Charcot-Marie-Tooth disease, causes failure in membrane integration, transport defects and rapid degradation. Multiple chaperones detect and remedy this aberrant behavior including the ER-membrane complex (EMC) which helps insert low-hydrophobicity TMSs (Coelho et al. 2019). If they fail to integrate, they are recognized by the ER-lumenal chaperone BiP. Ultimately, the E3 ligase gp78 ubiquitinates Cx32, targeting it for degradation. Thus, cells use a coordinated system of chaperones for membrane protein biogenesis. Dileucine-like motifs in the C-terminal tail of connexin32 control its endocytosis and assembly into gap junctions (Ray et al. 2018).

Animals

CX32 of Rattus norvegicus

Heteromeric connexin (Cx)32/Cx26; (CxB2, GJβ2, GJB2) (transports cAMP, cGMP and all inositol phosphates with 1-4 esterified phosphate groups (homomeric Cx26(β2) or homomeric Cx32 do not transport the inositol phosphates as well) (Ayad et al., 2006). The GJB2 gene encodes connexin 26, the protein involved in cell-cell attachment in many tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss as well as various skin disease phenotypes (Iossa et al., 2011; Tian et al. 2022). TMS1 regulates oligomerization and function (Jara et al., 2012).  The carboxyl tail pg Cx32 regulates gap junction assembly (Katoch et al. 2015).  In Cx46, neutralization of negative charges or addition of positive charge in the Cx26 equivalent region reduced the slow gate voltage dependence. In Cx50 the addition of a glutamate in the same region decreased the voltage dependence and the neutralization of a negative charge increased it. Thus, the charges at the end of TMS1 are part of the slow gate voltage sensor in Cxs. The fact that Cx42, which has no charge in this region, still presents voltage dependent slow gating suggests that charges still unidentified also contribute to the slow gate voltage sensitivity (Pinto et al. 2016).  Syndromic deafness mutations at Asn14 alter the open stability of Cx26 hemichannels (Sanchez et al. 2016). The Leu89Pro substitution in the second TMS of CX32 disrupts the trafficking of the protein, inhibiting the assembly of CX32 gap junctions, which in turn may result in peripheral neuropathy (Da et al. 2016).  Cx26 mutants that promote cell death or exert transdominant effects on other connexins in keratinocytes lead to skin diseases and hearing loss, whereas mutants having reduced channel function without aberrant effects on coexpressed connexins cause only hearing loss (Press et al. 2017). When challenged by a field of 0.06 V/nm, the Cx26 hemichannel relaxed toward a novel configuration characterized by a widened pore and an increased bending of the second TMS at the level of the conserved Pro87. A point mutation that inhibited such a transition impeded hemichannel opening in electrophysiology and dye uptake experiments.  Thus, the Cx26 hemichannel uses a global degree of freedom to transit between different configuration states, which may be shared among all connexins (Zonta et al. 2018). A group of human mutations within the N-terminal (NT) domain of connexin 26 hemichannels produce aberrant channel activity, which gives rise to deafness and skin disorders, including keratitis-ichthyosis-deafness (KID) syndrome. Structural and functional studies indicate that the NT domain of connexin hemichannels is folded into the pore, where it plays important roles in permeability and gating. The mutation, N14K disrupts cytosolic intersubunit interactions and promotes channel opening (Valdez Capuccino et al. 2018). A missense mutation in the Connexin 26 gene is associated with hereditary autosomal recessive sensorineural deafness (Leshinsky-Silver et al. 2005, Zytsar et al. 2020). Cx26 hemichannels mediate the passage of contents between the cytoplasm and extracellular space. To generate hemichannels, the mutation N176Y was introduced into the second extracellular loop of Cx26. The cryoEM structure of the hexameric hemichannel in lipid bilayer nanodiscs displays an open pore and a 4-helix bundle transmembrane design that is nearly identical to dodecameric GJCs. In contrast to the high resolution of the transmembrane alpha-helices, the extracellular loops are less well resolved. The conformational flexibility of the extracellular loops may be essential to facilitate surveillance of hemichannels in apposed cells to identify compatible Cx isoforms that enable intercellular docking (Khan et al. 2021). A rare variant c.516G>C (p.Trp172Cys) in the GJB2 (connexin 26) gene is associated with nonsyndromic hearing loss (Maslova et al. 2021). Keratitis-ichthyosis-deafness (KID) syndrome is caused by mutations in the GJB2 gene  (Asgari et al. 2020). An increase in the partial pressure of carbon dioxide (PCO₂) has been shown to cause Cx26 gap junctions to close. Cryo-EM was used to determine the structure of human Cx26 gap junctions under increasing levels of PCO₂. Brotherton et al. 2022 showed a correlation between the level of PCO₂ and the size of the aperture of the pore, governed by the N-terminal helices that line the pore. Thus, CO₂ alone is sufficient to cause conformational changes in the protein. Analysis of the conformational states showed that movements at the N-terminus are linked to both subunit rotation and flexing of the transmembrane helices (Brotherton et al. 2022). Cysteine residues in the C-terminal tail of connexin32 regulate its trafficking (Ray and Mehta 2021). The pathogenesis of common Gjb2 mutations are associated with human hereditary deafness (Li et al. 2023). Pan-cancer analysis of the prognostic and immunological role of GJB2 identifies a potential target for survival and immunotherapy (Jia et al. 2023).  The keratitis-ichthyosis-deafness (KID) syndrome is a rare genetic disease caused by pathogenic variants in connexin 26 (gene GJB2), which is a transmembrane channel of the epithelia (López-Sundh et al. 2023).  Consequences of pathogenic variants of the GJB2 gene (Cx26) localized in different Cx26 domains have been evaluated (Posukh et al. 2023). A pore locus in E1 of Cx26 and Cx30 impacts hemichannel functionality (Sanchez et al. 2024). An Ala/Glu difference in E1 of Cx26 and Cx30 contributes to their differential anionic permeabilities (Kraujaliene et al. 2024). Differential regulation of Cx26 hemichannels and gap junction channels by RhoA GTPase and the actin cytoskeleton has been observed (Jara et al. 2024).

Animals

Cx26/Cx32 of Homo sapiens
Cx26 (P29033)
Cx32 (P08034)

Heteromeric (or homomeric) Connexin46/Connexin50 junction (Cx46/Cx50; Cnx46/Cnx50; GJA8/GJA3) protein.  Mutations in CX46 or Cx50 cause cataracts, a cause of visual impairment and blindness (Derosa et al., 2007; Wang and Zhu 2012; Ye et al. 2019), and mutations in Cx46 can cause breast cancer (Grek et al. 2016). Cx43 and Cx46 regulate each other's expression and turnover in a reciprocal manner in addition to their conventional roles as gap junction proteins in lens cells (Banerjee et al., 2011).  The N-terminal half of connexin 46 appears to contain the core elements of the pore and voltage gates (Kronengold et al. 2012).  In Cx46, neutralization of negative charges or addition of positive charge in the Cx26 equivalent region reduced the slow gate voltage dependence. In Cx50 the addition of a glutamate in the same region decreased the voltage dependence, and the neutralization of a negative charge increased it. Thus, the charges at the end of TMS1 are part of the slow gate voltage sensor in Cxs. The fact that Cx42, which has no charge in this region, still presents voltage dependent slow gating, suggests that charges still unidentified also contribute to the slow gate voltage sensitivity (Pinto et al. 2016).  Cx43 is regulated by phosphorylation of Ser-373 (Puebla et al. 2016). A connexin50 mutation in the heterozygous state affects the lipid profile and the oxidative stress parameters in a spontaneously hypertensive rat strain (Šeda et al. 2016). Mutations in Cx50 (N220D and V44M) are responsible for congenital cataracts (Kuo et al. 2017; Zhang et al. 2018) Mutations its gene cause defects in early eye development (Ceroni et al. 2019). Cx50 is important for eye lens transparency, and calmoduin and Ca²⁺ cooperate in the gating control of Cx50 hemichannels (Zhang et al. 2006). Cx46 hemichannels are modulated by nitric oxide, and the fourth TMS cysteine may be involved in cataract formation (Retamal et al. 2019).  Gap19 is a Cx43 hemichannel inhibitor that acts as a gating modifier that decreases main state opening while increasing substate gating (Lissoni et al. 2020). Cx46, almost exclusively expressed in the eye lens, is upregulated in human breast cancer, and correlates with tumor growth (Acuña et al. 2020). EphA2 is required for normal Cx50 localization to the cell membrane, and conductance of lens fiber cells requires normal Eph-ephrin signaling and water channel (Aqp0) localization (Cheng et al. 2021). The Gja8 (Cx50) mutation gives rise to a cataract rat model (Shen et al. 2023). The V219F mutation in Gja8, induced semi-dominant nuclear cataracts. The p.V219F mutation altered Cx50 distribution, inhibited lens epithelial cell proliferation, migration, and adhesion, and disrupted fiber cell differentiation. As a consequence, the nuclear cataract and small lens formed (Shen et al. 2023). León-Fuentes et al. 2023 have reviewed the relationship between Cx46, its role in forming hemichannels and gap junctions, and its connection with cancer and cancer stem cells. Bioelectrical signal propagation involving Cx46 within the developing neuromuscular system is required for appropriate myofiber organization, and disruption leads to defects in behavior (Lukowicz-Bedford et al. 2023).

Animals

Cx46/Cx50 of Homo sapiens:
Cx46 (Q9Y6H8)
Cx50 (P48165)

Animals

Connexin37 of Homo sapiens (P35212)

Connexin 30 complex (connexin30.2/connexin31.3 (CX30.2/CX31.3)). Also called connexinΥ3/GJC3/GJε1; 279 aas, encoded by the GJB6 (13q12) gene (Cascella et al. 2016)). ATP is released from cells that stably expressed CX30.2 in a medium with low calcium, suggesting a hemichannel-based function. Liang et al. (2011) suggested that it shares functional properties with pannexin hemichannels rather than gap junction channels.  Defects cause nonsyndromic hypoacusia (hearing loss) due to partial loss of channel activity (Su et al. 2012; Su et al. 2013;  Cascella et al. 2016).  Cx30, but not Cx43, hemichannels close upon protein kinase C activation, showing that connexin hemichannels display not only isoform-specific permeability profiles but also isoform-specific regulation by PKC (Alstrom et al. 2015). The W77S mutant has a dominant negative effect on the formation and function of the gap junction and is probably responsible for hearing loss (Wong et al. 2017). Mutations in Cs30 rescue hearing and reveal roles for gap junctions in cochlear amplification (Lukashkina et al. 2017). The cryo-EM structure of the human Cx31.3/GJC3 connexin hemichannel has been solved (Lee et al. 2020). Cx31.3)/GJC3 hemichannels in the presence and absence of calcium ions and with a hearing-loss mutation R15G were solved at 2.3-, 2.5- and 2.6-Å resolutions, respectively. Compared with available structures of GJICh in the open conformation, the Cx31.3 hemichannel shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion-binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. The hemichannel has a pore with a diameter of ~8 Å and selectively transports chloride ions (Lee et al. 2020).  A pore locus in E1 of Cx26 and Cx30 impacts hemichannel functionality (Sanchez et al. 2024).  An Ala/Glu difference in E1 of Cx26 and Cx30 contributes to their differential anionic permeabilities (Kraujaliene et al. 2024).

Animals

Cx30.2 of Homo sapiens (Q8NFK1)

Connexin40 (Cx40; Gap Junction Protein δ4; GJδ4) of 370 aas and 4 TM (Kopanic et al. 2015).

Animals

Cx40 of Homo sapiens

Gap junction epsilon-1 protein, Gjf1 of 205 aas and 4 TMSs.  Mutations result in variable small eyes and affect lens development (Puk et al. 2008).

Gjf1 of Mus musculus

Invertebrate cordate Connexin 47 (White et al., 2004).

Tunicates

Connexin 47 of Halocynthia pyriformis (Q6U1M0)

Inverebrate cordate Connexin (Hervé et al., 2005).

Tunicates

Connexin of Oikopleura dioica (E4YIP4)

Connexin45 (Cx45; Cx-45; Gap Junction protein γ1; GJγ1; Gjc1; Gja7; CxG1) of 396 aas and 4 TMSs (Kopanic et al. 2015).

Animals

Cx45 of Homo sapiens