Gephyrin
| Gephyrin | ||
|---|---|---|
|
||
| Properties of human protein | ||
| Mass / length primary structure | 736 amino acids | |
| Secondary to quaternary structure | Homotrimer | |
| Cofactor | magnesium | |
| Isoforms | 2 | |
| Identifier | ||
| Gene name | GPHN | |
| External IDs | ||
| Enzyme Classifications | ||
| EC, category | 2.7.7.5 , Transferase | |
| Response type | Transfer of an AMP remainder | |
| Substrate | Molybdopterin (Cu) + ATP | |
| Products | Adenylyl molybdopterin + PP i | |
| EC, category | 2.10.1.1 , transferase | |
| Response type | Transfer of a molybdenum ion | |
| Substrate | Adenylyl molybdopterin + molybdate | |
| Products | Molybdenum cofactor (desulfurized) + AMP | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 10243 | 268566 |
| Ensemble | ENSG00000171723 | ENSMUSG00000047454 |
| UniProt | Q9NQX3 | Q8BUV3 |
| Refseq (mRNA) | NM_001024218 | NM_145965 |
| Refseq (protein) | NP_001019389 | NP_666077 |
| Gene locus | Chr 14: 66.51 - 67.18 Mb | Chr 12: 78.23 - 78.68 Mb |
| PubMed search | 10243 |
268566
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Gephyrin is a multifunctional enzyme in all eukaryotes that catalyzes two steps in molybdenum cofactor biosynthesis . It also functions as a structural protein in inhibitory postsynapses in animals . Mutations in GPHN - gene of the people can the enzyme deficiency and so on rare genetic disease molybdenum cofactor deficiency lead.
Catalyzed reactions
Overall, the following reaction is catalyzed, the intermediate step is not displayed:
+ ATP + MoO 4 2− + AMP + PP i + Cu 2+
Molybdopterin (Cu) is converted with molybdate to MoCo, ATP is consumed. The MoCo is desulfurized and can only be used by special enzymes.
Function in the cell structure
Analogous to the PSD-95 on excitatory synapses, gephyrin is considered to be a crucial structural element for the organization of the postsynapse. Gephyrin was discovered through its binding to glycine receptors , which mainly inhibit nerve cells in the spinal cord and brain stem . But it also binds directly to GABA receptors , the most important inhibitory receptors in the rest of the central nervous system .
In cells, gephyrin is usually present as an oligomer ; the basis appears to be a trimeric conformation. Different splice variants prevent this oligomerization without affecting the binding to the receptors. Nevertheless, they disrupt the composition of the inhibitory postsynapse and can play a role in diseases such as epilepsy .
In some forms of experimentally induced epilepsy, the gephyrin levels change significantly. In the animal model, complete gephyrin deficiency leads to stiff muscles and death immediately after birth. Stiff muscles are also a symptom of hypereplexia and stiff person syndrome , and are not adequately inhibited in either disease. The cause can be a mutation in the gephyrin gene or the deactivation of the protein by auto-antibodies .
literature
- V. Tretter, J. Mukherjee u. a .: Gephyrin, the enigmatic organizer at GABAergic synapses. In: Frontiers in cellular neuroscience. Volume 6, 2012, p. 23, doi: 10.3389 / fncel.2012.00023 . PMID 22615685 . PMC 3351755 (free full text).
