Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 105  species 0  interactions 119  sequences 3  architectures

Family: Connexin50 (PF03509)

Summary: Gap junction alpha-8 protein (Cx50)

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "GJA8". More...

GJA8 Edit Wikipedia article

GJA8
Identifiers
Aliases GJA8, CAE, CAE1, CTRCT1, CX50, CZP1, MP70, gap junction protein alpha 8
External IDs MGI: 99953 HomoloGene: 3857 GeneCards: GJA8
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for GJA8
Genomic location for GJA8
Band 1q21.2 Start 147,907,956 bp[1]
End 147,909,257 bp[1]
RNA expression pattern
PBB GE GJA8 208489 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005267

NM_008123

RefSeq (protein)

NP_005258

NP_032149

Location (UCSC) Chr 1: 147.91 – 147.91 Mb Chr 1: 96.91 – 96.93 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Connexin50
Identifiers
Symbol Connexin50
Pfam PF03509
InterPro IPR002266

Gap junction alpha-8 protein is a protein that in humans is encoded by the GJA8 gene.[5][6][7] It is also known as connexin 50.

Related gene problems

Interactions

GJA8 has been shown to interact with Tight junction protein 1.[10]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121634 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049908 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Shiels A, Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S (Apr 1998). "A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q". Am J Hum Genet. 62 (3): 526–32. doi:10.1086/301762. PMC 1376956Freely accessible. PMID 9497259. 
  6. ^ Church RL, Wang JH, Steele E (Aug 1995). "The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal analysis and chromosome mapping". Curr Eye Res. 14 (3): 215–21. doi:10.3109/02713689509033517. PMID 7796604. 
  7. ^ "Entrez Gene: GJA8 gap junction protein, alpha 8, 50kDa". 
  8. ^ a b Mefford HC, Sharp AJ, Baker C, Itsara A, Jiang Z, Buysse K, Huang S, Maloney VK, Crolla JA, Baralle D, et al. (October 2008). "Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes". N. Engl. J. Med. 359 (16): 1685–99. doi:10.1056/NEJMoa0805384. PMC 2703742Freely accessible. PMID 18784092. 
  9. ^ Rong P, Wang X, Niesman I, Wu Y, Benedetti LE, Dunia I, Levy E, Gong X (January 2002). "Disruption of Gja8 (alpha8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation". Development. 129 (1): 167–74. PMID 11782410. 
  10. ^ Nielsen PA, Baruch A, Shestopalov VI, Giepmans BN, Dunia I, Benedetti EL, Kumar NM (June 2003). "Lens connexins alpha3Cx46 and alpha8Cx50 interact with zonula occludens protein-1 (ZO-1)". Mol. Biol. Cell. 14 (6): 2470–81. doi:10.1091/mbc.E02-10-0637. PMC 194895Freely accessible. PMID 12808044. 

Further reading


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.

Gap junction alpha-8 protein (Cx50) Provide feedback

No Pfam abstract.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002266

The connexins are a family of integral membrane proteins that oligomerise to form intercellular channels that are clustered at gap junctions. These channels are specialised sites of cell-cell contact that allow the passage of ions, intracellular metabolites and messenger molecules (with molecular weight less than 1-2kDa) from the cytoplasm of one cell to its opposing neighbours. They are found in almost all vertebrate cell types, and somewhat similar proteins have been cloned from plant species. Invertebrates utilise a different family of molecules, innexins, that share a similar predicted secondary structure to the vertebrate connexins, but have no sequence identity to them [PUBMED:9769729].

Vertebrate gap junction channels are thought to participate in diverse biological functions. For instance, in the heart they permit the rapid cell-cell transfer of action potentials, ensuring coordinated contraction of the cardiomyocytes. They are also responsible for neurotransmission at specialised 'electrical' synapses. In non-excitable tissues, such as the liver, they may allow metabolic cooperation between cells. In the brain, glial cells are extensively-coupled by gap junctions; this allows waves of intracellular Ca2+ to propagate through nervous tissue, and may contribute to their ability to spatially-buffer local changes in extracellular K+ concentration [PUBMED:7685944].

The connexin protein family is encoded by at least 13 genes in rodents, with many homologues cloned from other species. They show overlapping tissue expression patterns, most tissues expressing more than one connexin type. Their conductances, permeability to different molecules, phosphorylation and voltage-dependence of their gating, have been found to vary. Possible communication diversity is increased further by the fact that gap junctions may be formed by the association of different connexin isoforms from apposing cells. However, in vitro studies have shown that not all possible combinations of connexins produce active channels [PUBMED:8811187, PUBMED:8608591].

Hydropathy analysis predicts that all cloned connexins share a common transmembrane (TM) topology. Each connexin is thought to contain 4 TM domains, with two extracellular and three cytoplasmic regions. This model has been validated for several of the family members by in vitro biochemical analysis. Both N- and C-termini are thought to face the cytoplasm, and the third TM domain has an amphipathic character, suggesting that it contributes to the lining of the formed-channel. Amino acid sequence identity between the isoforms is ~50-80%, with the TM domains being well conserved. Both extracellular loops contain characteristically conserved cysteine residues, which likely form intramolecular disulphide bonds. By contrast, the single putative intracellular loop (between TM domains 2 and 3) and the cytoplasmic C terminus are highly variable among the family members. Six connexins are thought to associate to form a hemi-channel, or connexon. Two connexons then interact (likely via the extracellular loops of their connexins) to form the complete gap junction channel.

 
       NH2-***        ***        *************-COOH
             **     **   **      **
             **    **     **    **   Cytoplasmic
          ---**----**-----**----**----------------
             **    **     **    **   Membrane
             **    **     **    **
          ---**----**-----**----**----------------
             **    **     **    **   Extracellular
              **  **       **  **
                **           **

Two sets of nomenclature have been used to identify the connexins. The first, and most commonly used, classifies the connexin molecules according to molecular weight, such as connexin43 (abbreviated to Cx43), indicating a connexin of molecular weight close to 43kDa. However, studies have revealed cases where clear functional homologues exist across species that have quite different molecular masses; therefore, an alternative nomenclature was proposed based on evolutionary considerations, which divides the family into two major subclasses, alpha and beta, each with a number of members [PUBMED:1320430]. Due to their ubiquity and overlapping tissue distributions, it has proved difficult to elucidate the functions of individual connexin isoforms. To circumvent this problem, particular connexin-encoding genes have been subjected to targeted-disruption in mice, and the phenotype of the resulting animals investigated. Around half the connexin isoforms have been investigated in this manner [PUBMED:9861669]. Further insight into the functional roles of connexins has come from the discovery that a number of human diseases are caused by mutations in connexin genes. For instance, mutations in Cx32 give rise to a form of inherited peripheral neuropathy called X-linked dominant Charcot-Marie-Tooth disease [PUBMED:7570999]. Similarly, mutations in Cx26 are responsible for both autosomal recessive and dominant forms of nonsyndromic deafness, a disorder characterised by hearing loss, with no apparent effects on other organ systems.

Gap junction alpha-8 protein (also called connexin50, Cx50, or lens fibre protein MP70) is a connexin of ~431 amino acid residues. The chicken isoform is shorter (399 residues) and is hence known as Cx45.6. Cx50 and Cx46 are the two gap junction proteins normally found in lens fibre cells of the eye. Evidence from both genetically-engineered mice, and from the identification of mutations in the human Cx50-encoding gene, highlight the importance of this connexin in maintaining lens transparency. Deletion of mice Cx50 produces a viable phenotype, but these animals start to develop cataracts (of the zonular pulverant type) at about one week old. They also have abnormally small eyes and lenses. Similarly, mutations in the human gene encoding Cx50 have been associated with the occurrence of congenital cataracts. Affected individuals develop cataracts (with zonular pulverent opacities), and analysis shows they have a single point mutation in the Cx50 coding region, resulting in a non-conservative substitution in the second putative TM domain of a serine residue for a proline.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

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...

View options

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
(11)
Full
(119)
Representative proteomes UniProt
(171)
NCBI
(351)
Meta
(0)
RP15
(11)
RP35
(37)
RP55
(99)
RP75
(119)
Jalview View  View  View  View  View  View  View  View   
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(11)
Full
(119)
Representative proteomes UniProt
(171)
NCBI
(351)
Meta
(0)
RP15
(11)
RP35
(37)
RP55
(99)
RP75
(119)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(11)
Full
(119)
Representative proteomes UniProt
(171)
NCBI
(351)
Meta
(0)
RP15
(11)
RP35
(37)
RP55
(99)
RP75
(119)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped 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.

Note: You can also download the data file for the tree.

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: PRINTS
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Griffiths-Jones SR
Number in seed: 11
Number in full: 119
Average length of the domain: 65.70 aa
Average identity of full alignment: 70 %
Average coverage of the sequence by the domain: 15.46 %

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 25.0 25.0
Trusted cut-off 42.7 40.9
Noise cut-off 21.6 20.6
Model length: 66
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.