Q9NQX3 · GEPH_HUMAN
- ProteinGephyrin
- GeneGPHN
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids736 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity).
Acts as a major instructive molecule at inhibitory synapses, where it also clusters GABA type A receptors (PubMed:25025157, PubMed:26613940).
Acts as a major instructive molecule at inhibitory synapses, where it also clusters GABA type A receptors (PubMed:25025157, PubMed:26613940).
Has also a catalytic activity and catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.
Catalytic activity
- ATP + H+ + molybdopterin = adenylyl-molybdopterin + diphosphateThis reaction proceeds in the forward direction.
Cofactor
Activity regulation
Inhibited by copper and tungsten.
Pathway
Cofactor biosynthesis; molybdopterin biosynthesis.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGephyrin
Including 2 domains:
- Recommended nameMolybdopterin adenylyltransferase
- EC number
- Short namesMPT adenylyltransferase
- Alternative names
- Recommended nameMolybdopterin molybdenumtransferase
- EC number
- Short namesMPT Mo-transferase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NQX3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Postsynaptic cell membrane ; Lipid-anchor
Cell membrane ; Lipid-anchor
Note: Cytoplasmic face of glycinergic postsynaptic membranes (By similarity).
Forms clusters at synapses (PubMed:25025157).
Forms clusters at synapses (PubMed:25025157).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Molybdenum cofactor deficiency C (MOCODC)
- Note
- DescriptionA form of molybdenum cofactor deficiency, an autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients.
- See alsoMIM:615501
Natural variants in MOCODC
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_075626 | 375 | G>D | in MOCODC; patient phenotype resembling Dravet syndrome; abolishes postsynaptic clustering of GPHN; decreases cell-surface expression of GABA receptors; impairs postsynaptic currents; catalytically inactive; decreases binding affinity toward GABRA3; decreases binding affinity toward GLRB | |
VAR_070275 | 580 | D>A | in MOCODC; lacks molybdenum cofactor synthesis activity; dbSNP:rs397518420 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_044162 | 10 | found in a patient with hyperekplexia; uncertain significance; does not disrupt GLRB-GPHN interactions; does not affect the structural lattices formed by GPHN; dbSNP:rs121908539 | |||
Sequence: N → Y | ||||||
Mutagenesis | 212 | Decreased palmitoylation. Decreased clustering at synaptic membranes. Decreased function in gamma-aminobutyric acid receptor clustering. Loss of palmitoylation, decreased clustering at synaptic membranes and loss of function in gamma-aminobutyric acid receptor clustering; when associated with S-284. | ||||
Sequence: C → S | ||||||
Mutagenesis | 284 | Decreased palmitoylation. Decreased clustering at synaptic membranes. Decreased function in gamma-aminobutyric acid receptor clustering. Loss of palmitoylation, decreased clustering at synaptic membranes and loss of function in gamma-aminobutyric acid receptor clustering; when associated with S-212. | ||||
Sequence: C → S | ||||||
Natural variant | VAR_075626 | 375 | in MOCODC; patient phenotype resembling Dravet syndrome; abolishes postsynaptic clustering of GPHN; decreases cell-surface expression of GABA receptors; impairs postsynaptic currents; catalytically inactive; decreases binding affinity toward GABRA3; decreases binding affinity toward GLRB | |||
Sequence: G → D | ||||||
Natural variant | VAR_070275 | 580 | in MOCODC; lacks molybdenum cofactor synthesis activity; dbSNP:rs397518420 | |||
Sequence: D → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 762 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data), lipidation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000170964 | 1-736 | UniProt | Gephyrin | |||
Sequence: MATEGMILTNHDHQIRVGVLTVSDSCFRNLAEDRSGINLKDLVQDPSLLGGTISAYKIVPDEIEEIKETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSLNVTPLGMLSRPVCGIRGKTLIINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVHDELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDSSSSHITAAAIAAKIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTPKVQSRCSSKENILRASHSAVDITKVARRHRMSPFPLTSMDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVYAKDNLPPFPASVKDGYAVRAADGPGDRFIIGESQAGEQPTQTVMPGQVMRVTTGAPIPCGADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRGECVLAKGTHMGPSEIGLLATVGVTEVEVNKFPVVAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYPTINLGIVGDNPDDLLNALNEGISRADVIITSGGVSMGEKDYLKQVLDIDLHAQIHFGRVFMKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQGILDPRPTIIKARLSCDVKLDPRPEYHRCILTWHHQEPLPWAQSTGNQMSSRLMSMRSANGLLMLPPKTEQYVELHKGEVVDVMVIGRL | |||||||
Modified residue | 188 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 188 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 194 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 194 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 198 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 198 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 200 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 200 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Lipidation | 212 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Modified residue | 262 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 262 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 264 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 265 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 266 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 266 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 268 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 268 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 270 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 270 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 280 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 281 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 283 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Lipidation | 284 | UniProt | S-palmitoyl cysteine | ||||
Sequence: C | |||||||
Modified residue (large scale data) | 286 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 295 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 303 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 305 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 305 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Palmitoylated (PubMed:25025157).
Palmitoylation is stimulated by GABA type A receptors activity (By similarity).
Palmitoylation by ZDHHC12 regulates clustering at synapses (PubMed:25025157).
Palmitoylation is stimulated by GABA type A receptors activity (By similarity).
Palmitoylation by ZDHHC12 regulates clustering at synapses (PubMed:25025157).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homotrimer, homodimer and homooligomer (PubMed:26613940).
Interacts with GABARAP (By similarity).
Interacts with SRGAP2 (via SH3 domain) (By similarity).
Interacts with GABRA3 (PubMed:26613940).
Interacts with GLRB (PubMed:12684523, PubMed:26613940).
GABRA3 and GLRB occupy overlapping binding sites (By similarity).
Interacts with ARHGAP32; IQSEC3, INSYN1 and INSYN2A (By similarity).
Interacts with GABARAP (By similarity).
Interacts with SRGAP2 (via SH3 domain) (By similarity).
Interacts with GABRA3 (PubMed:26613940).
Interacts with GLRB (PubMed:12684523, PubMed:26613940).
GABRA3 and GLRB occupy overlapping binding sites (By similarity).
Interacts with ARHGAP32; IQSEC3, INSYN1 and INSYN2A (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NQX3 | DYNLL1 P63167 | 4 | EBI-2371891, EBI-349105 | |
BINARY | Q9NQX3-2 | MITD1 Q8WV92 | 3 | EBI-11043087, EBI-2691489 | |
BINARY | Q9NQX3-2 | PSMA1 P25786 | 3 | EBI-11043087, EBI-359352 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 14-166 | MPT Mo-transferase | ||||
Sequence: QIRVGVLTVSDSCFRNLAEDRSGINLKDLVQDPSLLGGTISAYKIVPDEIEEIKETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSLNVTPLGMLSRPVCGIRGKTLIINLPGSKKGSQECFQFILPALPHAI | ||||||
Region | 140-316 | Interaction with GABARAP | ||||
Sequence: LIINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVHDELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDSSSSHITAAAIAAKIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTPKVQSRCSSKENILRASHSAVDITKVARRH | ||||||
Region | 181-232 | Disordered | ||||
Sequence: DELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDSSS | ||||||
Compositional bias | 206-225 | Basic and acidic residues | ||||
Sequence: EDKGVQCEEEEEEKKDSGVA | ||||||
Region | 260-290 | Disordered | ||||
Sequence: TASLSTTPSESPRAQATSRLSTASCPTPKVQ | ||||||
Region | 326-736 | MPT adenylyltransferase | ||||
Sequence: MDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVYAKDNLPPFPASVKDGYAVRAADGPGDRFIIGESQAGEQPTQTVMPGQVMRVTTGAPIPCGADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRGECVLAKGTHMGPSEIGLLATVGVTEVEVNKFPVVAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYPTINLGIVGDNPDDLLNALNEGISRADVIITSGGVSMGEKDYLKQVLDIDLHAQIHFGRVFMKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQGILDPRPTIIKARLSCDVKLDPRPEYHRCILTWHHQEPLPWAQSTGNQMSSRLMSMRSANGLLMLPPKTEQYVELHKGEVVDVMVIGRL |
Sequence similarities
In the N-terminal section; belongs to the MoaB/Mog family.
In the C-terminal section; belongs to the MoeA family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9NQX3-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length736
- Mass (Da)79,748
- Last updated2000-10-01 v1
- ChecksumE2BDA3AD3AB962C0
Q9NQX3-2
- Name2
- Differences from canonical
- 243-243: K → KKHPFYTSPAVVMAHGEQPIPGLINYSHHSTDER
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 206-225 | Basic and acidic residues | ||||
Sequence: EDKGVQCEEEEEEKKDSGVA | ||||||
Alternative sequence | VSP_021769 | 243 | in isoform 2 | |||
Sequence: K → KKHPFYTSPAVVMAHGEQPIPGLINYSHHSTDER | ||||||
Sequence conflict | 261 | in Ref. 1; CAC81240 | ||||
Sequence: A → V |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ272033 EMBL· GenBank· DDBJ | CAC81240.1 EMBL· GenBank· DDBJ | mRNA | ||
AF272663 EMBL· GenBank· DDBJ | AAF81785.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ272343 EMBL· GenBank· DDBJ | CAC10537.1 EMBL· GenBank· DDBJ | mRNA | ||
AB037806 EMBL· GenBank· DDBJ | BAA92623.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC030016 EMBL· GenBank· DDBJ | AAH30016.1 EMBL· GenBank· DDBJ | mRNA |