ID GEPH_HUMAN Reviewed; 736 AA. AC Q9NQX3; Q96KU4; Q9H4E9; Q9P2G2; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 206. DE RecName: Full=Gephyrin {ECO:0000303|PubMed:10839351}; DE Includes: DE RecName: Full=Molybdopterin adenylyltransferase; DE Short=MPT adenylyltransferase; DE EC=2.7.7.75 {ECO:0000305|PubMed:26613940}; DE AltName: Full=Domain G; DE Includes: DE RecName: Full=Molybdopterin molybdenumtransferase; DE Short=MPT Mo-transferase; DE EC=2.10.1.1 {ECO:0000305|PubMed:22040219, ECO:0000305|PubMed:26613940}; DE AltName: Full=Domain E; GN Name=GPHN {ECO:0000312|HGNC:HGNC:15465}; Synonyms=GPH, KIAA1385; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hippocampus; RX PubMed=10839351; DOI=10.1016/s0896-6273(00)81165-4; RA Butler M.H., Hayashi A., Okoshi N., Villmann C., Becker C.M., Feng G., RA De Camilli P., Solimena M.; RT "Autoimmunity to gephyrin in Stiff-Man syndrome."; RL Neuron 26:307-312(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN MOCODC, AND PATHWAY. RX PubMed=11095995; DOI=10.1086/316941; RA Reiss J., Gross-Hardt S., Christensen E., Schmidt P., Mendel R.R., RA Schwarz G.; RT "A mutation in the gene for the neurotransmitter receptor-clustering RT protein gephyrin causes a novel form of molybdenum cofactor deficiency."; RL Am. J. Hum. Genet. 68:208-213(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Kidney; RX PubMed=11418245; DOI=10.1016/s0378-1119(01)00511-x; RA David-Watine B.; RT "The human gephyrin (GPHN) gene: structure, chromosome localization and RT expression in non-neuronal cells."; RL Gene 271:239-245(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-266, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-194, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-194, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188; SER-194; THR-198 AND RP SER-305, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, PALMITOYLATION AT CYS-212 AND RP CYS-284, AND MUTAGENESIS OF CYS-212 AND CYS-284. RX PubMed=25025157; DOI=10.1371/journal.pbio.1001908; RA Dejanovic B., Semtner M., Ebert S., Lamkemeyer T., Neuser F., Luescher B., RA Meier J.C., Schwarz G.; RT "Palmitoylation of gephyrin controls receptor clustering and plasticity of RT GABAergic synapses."; RL PLoS Biol. 12:e1001908-e1001908(2014). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-181, AND SUBUNIT. RX PubMed=11554796; DOI=10.1006/jmbi.2001.4952; RA Schwarz G., Schrader N., Mendel R.R., Hecht H.-J., Schindelin H.; RT "Crystal structures of human gephyrin and plant Cnx1 G domains: comparative RT analysis and functional implications."; RL J. Mol. Biol. 312:405-418(2001). RN [16] RP VARIANT TYR-10, CHARACTERIZATION OF VARIANT TYR-10, AND INTERACTION WITH RP GLRB. RX PubMed=12684523; DOI=10.1074/jbc.m301070200; RA Rees M.I., Harvey K., Ward H., White J.H., Evans L., Duguid I.C., RA Hsu C.-C., Coleman S.L., Miller J., Baer K., Waldvogel H.J., Gibbon F., RA Smart T.G., Owen M.J., Harvey R.J., Snell R.G.; RT "Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains RT to the glycine receptor, and mutation analysis in hyperekplexia."; RL J. Biol. Chem. 278:24688-24696(2003). RN [17] RP VARIANT MOCODC ALA-580, AND PATHWAY. RX PubMed=22040219; DOI=10.1111/j.1399-0004.2011.01709.x; RA Reiss J., Lenz U., Aquaviva-Bourdain C., Joriot-Chekaf S., RA Mention-Mulliez K., Holder-Espinasse M.; RT "A GPHN point mutation leading to molybdenum cofactor deficiency."; RL Clin. Genet. 80:598-599(2011). RN [18] RP VARIANT MOCODC ASP-375, CHARACTERIZATION OF MOCODC VARIANTS ASP-375 AND RP ALA-580, INTERACTION WITH GABRA3 AND GLRB, SUBCELLULAR LOCATION, SUBUNIT, RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=26613940; DOI=10.15252/emmm.201505323; RG EuroEPINOMICS Dravet working group; RA Dejanovic B., Djemie T., Gruenewald N., Suls A., Kress V., Hetsch F., RA Craiu D., Zemel M., Gormley P., Lal D., Myers C.T., Mefford H.C., RA Palotie A., Helbig I., Meier J.C., De Jonghe P., Weckhuysen S., Schwarz G.; RT "Simultaneous impairment of neuronal and metabolic function of mutated RT gephyrin in a patient with epileptic encephalopathy."; RL EMBO Mol. Med. 7:1580-1594(2015). CC -!- FUNCTION: Microtubule-associated protein involved in membrane protein- CC cytoskeleton interactions. It is thought to anchor the inhibitory CC glycine receptor (GLYR) to subsynaptic microtubules (By similarity). CC Acts as a major instructive molecule at inhibitory synapses, where it CC also clusters GABA type A receptors (PubMed:25025157, PubMed:26613940). CC {ECO:0000250|UniProtKB:Q03555, ECO:0000269|PubMed:25025157, CC ECO:0000269|PubMed:26613940}. CC -!- FUNCTION: Has also a catalytic activity and catalyzes two steps in the CC biosynthesis of the molybdenum cofactor. In the first step, CC molybdopterin is adenylated. Subsequently, molybdate is inserted into CC adenylated molybdopterin and AMP is released. CC {ECO:0000269|PubMed:26613940}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H(+) + molybdopterin = adenylyl-molybdopterin + CC diphosphate; Xref=Rhea:RHEA:31331, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58698, CC ChEBI:CHEBI:62727; EC=2.7.7.75; CC Evidence={ECO:0000305|PubMed:26613940}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31332; CC Evidence={ECO:0000305|PubMed:26613940}; CC -!- CATALYTIC ACTIVITY: CC Reaction=adenylyl-molybdopterin + H(+) + molybdate = AMP + H2O + Mo- CC molybdopterin; Xref=Rhea:RHEA:35047, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36264, ChEBI:CHEBI:62727, CC ChEBI:CHEBI:71302, ChEBI:CHEBI:456215; EC=2.10.1.1; CC Evidence={ECO:0000305|PubMed:22040219, ECO:0000305|PubMed:26613940}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35048; CC Evidence={ECO:0000305|PubMed:22040219, ECO:0000305|PubMed:26613940}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Inhibited by copper and tungsten. {ECO:0000250}. CC -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis. CC {ECO:0000269|PubMed:11095995, ECO:0000269|PubMed:22040219, CC ECO:0000269|PubMed:26613940}. CC -!- SUBUNIT: Homotrimer, homodimer and homooligomer (PubMed:26613940). CC Interacts with GABARAP (By similarity). Interacts with SRGAP2 (via SH3 CC domain) (By similarity). Interacts with GABRA3 (PubMed:26613940). CC Interacts with GLRB (PubMed:26613940, PubMed:12684523). GABRA3 and GLRB CC occupy overlapping binding sites (By similarity). Interacts with CC ARHGAP32; IQSEC3, INSYN1 and INSYN2A (By similarity). CC {ECO:0000250|UniProtKB:Q03555, ECO:0000250|UniProtKB:Q8BUV3, CC ECO:0000269|PubMed:12684523, ECO:0000269|PubMed:26613940}. CC -!- INTERACTION: CC Q9NQX3; P63167: DYNLL1; NbExp=2; IntAct=EBI-2371891, EBI-349105; CC Q9NQX3-2; Q8WV92: MITD1; NbExp=3; IntAct=EBI-11043087, EBI-2691489; CC Q9NQX3-2; P25786: PSMA1; NbExp=3; IntAct=EBI-11043087, EBI-359352; CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane CC {ECO:0000269|PubMed:25025157, ECO:0000269|PubMed:26613940}; Lipid- CC anchor {ECO:0000269|PubMed:25025157}; Cytoplasmic side CC {ECO:0000305|PubMed:25025157}. Cell membrane CC {ECO:0000250|UniProtKB:Q03555}; Lipid-anchor CC {ECO:0000250|UniProtKB:Q03555}; Cytoplasmic side CC {ECO:0000250|UniProtKB:Q03555}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:25025157}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q03555}. Cell projection, dendrite CC {ECO:0000269|PubMed:26613940}. Postsynaptic density CC {ECO:0000250|UniProtKB:Q8BUV3}. Note=Cytoplasmic face of glycinergic CC postsynaptic membranes (By similarity). Forms clusters at synapses CC (PubMed:25025157). {ECO:0000250|UniProtKB:Q03555, CC ECO:0000269|PubMed:25025157}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NQX3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NQX3-2; Sequence=VSP_021769; CC -!- PTM: Palmitoylated (PubMed:25025157). Palmitoylation is stimulated by CC GABA type A receptors activity (By similarity). Palmitoylation by CC ZDHHC12 regulates clustering at synapses (PubMed:25025157). CC {ECO:0000250|UniProtKB:Q8BUV3, ECO:0000269|PubMed:25025157}. CC -!- DISEASE: Molybdenum cofactor deficiency, complementation group C CC (MOCODC) [MIM:615501]: A form of molybdenum cofactor deficiency, an CC autosomal recessive metabolic disorder leading to the pleiotropic loss CC of molybdoenzyme activities. It is clinically characterized by onset in CC infancy of poor feeding, intractable seizures, severe psychomotor CC retardation, and death in early childhood in most patients. CC {ECO:0000269|PubMed:11095995, ECO:0000269|PubMed:22040219, CC ECO:0000269|PubMed:26613940}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: In the N-terminal section; belongs to the MoaB/Mog family. CC {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the MoeA family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA92623.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/317/GPHN"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ272033; CAC81240.1; -; mRNA. DR EMBL; AF272663; AAF81785.1; -; mRNA. DR EMBL; AJ272343; CAC10537.1; -; mRNA. DR EMBL; AB037806; BAA92623.1; ALT_INIT; mRNA. DR EMBL; BC030016; AAH30016.1; -; mRNA. DR CCDS; CCDS32103.1; -. [Q9NQX3-1] DR CCDS; CCDS9777.1; -. [Q9NQX3-2] DR RefSeq; NP_001019389.1; NM_001024218.1. [Q9NQX3-1] DR RefSeq; NP_065857.1; NM_020806.4. [Q9NQX3-2] DR PDB; 1JLJ; X-ray; 1.60 A; A/B/C=1-181. DR PDBsum; 1JLJ; -. DR AlphaFoldDB; Q9NQX3; -. DR SMR; Q9NQX3; -. DR BioGRID; 115537; 75. DR DIP; DIP-41076N; -. DR IntAct; Q9NQX3; 28. DR MINT; Q9NQX3; -. DR STRING; 9606.ENSP00000417901; -. DR DrugBank; DB01942; Formic acid. DR DrugBank; DB03366; Imidazole. DR DrugBank; DB03766; Propanoic acid. DR MoonDB; Q9NQX3; Curated. DR MoonProt; Q9NQX3; -. DR GlyCosmos; Q9NQX3; 2 sites, 1 glycan. DR GlyGen; Q9NQX3; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q9NQX3; -. DR PhosphoSitePlus; Q9NQX3; -. DR BioMuta; GPHN; -. DR DMDM; 13431554; -. DR EPD; Q9NQX3; -. DR jPOST; Q9NQX3; -. DR MassIVE; Q9NQX3; -. DR MaxQB; Q9NQX3; -. DR PaxDb; 9606-ENSP00000417901; -. DR PeptideAtlas; Q9NQX3; -. DR ProteomicsDB; 82221; -. [Q9NQX3-1] DR ProteomicsDB; 82222; -. [Q9NQX3-2] DR Pumba; Q9NQX3; -. DR ABCD; Q9NQX3; 9 sequenced antibodies. DR Antibodypedia; 144; 490 antibodies from 38 providers. DR DNASU; 10243; -. DR Ensembl; ENST00000315266.9; ENSP00000312771.5; ENSG00000171723.16. [Q9NQX3-1] DR Ensembl; ENST00000478722.6; ENSP00000417901.1; ENSG00000171723.16. [Q9NQX3-2] DR GeneID; 10243; -. DR KEGG; hsa:10243; -. DR MANE-Select; ENST00000478722.6; ENSP00000417901.1; NM_020806.5; NP_065857.1. [Q9NQX3-2] DR UCSC; uc001xix.4; human. [Q9NQX3-1] DR AGR; HGNC:15465; -. DR CTD; 10243; -. DR DisGeNET; 10243; -. DR GeneCards; GPHN; -. DR GeneReviews; GPHN; -. DR HGNC; HGNC:15465; GPHN. DR HPA; ENSG00000171723; Tissue enhanced (brain, liver). DR MalaCards; GPHN; -. DR MIM; 603930; gene. DR MIM; 615501; phenotype. DR neXtProt; NX_Q9NQX3; -. DR OpenTargets; ENSG00000171723; -. DR Orphanet; 3197; Hereditary hyperekplexia. DR Orphanet; 308400; Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C. DR PharmGKB; PA28840; -. DR VEuPathDB; HostDB:ENSG00000171723; -. DR eggNOG; KOG2371; Eukaryota. DR GeneTree; ENSGT00390000016577; -. DR HOGENOM; CLU_010186_2_2_1; -. DR InParanoid; Q9NQX3; -. DR OMA; ESPYPMI; -. DR OrthoDB; 275356at2759; -. DR PhylomeDB; Q9NQX3; -. DR TreeFam; TF300902; -. DR BioCyc; MetaCyc:ENSG00000171723-MONOMER; -. DR PathwayCommons; Q9NQX3; -. DR Reactome; R-HSA-947581; Molybdenum cofactor biosynthesis. DR SignaLink; Q9NQX3; -. DR SIGNOR; Q9NQX3; -. DR UniPathway; UPA00344; -. DR BioGRID-ORCS; 10243; 12 hits in 1158 CRISPR screens. DR ChiTaRS; GPHN; human. DR EvolutionaryTrace; Q9NQX3; -. DR GeneWiki; GPHN; -. DR GenomeRNAi; 10243; -. DR Pharos; Q9NQX3; Tbio. DR PRO; PR:Q9NQX3; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9NQX3; Protein. DR Bgee; ENSG00000171723; Expressed in cerebellar cortex and 178 other cell types or tissues. DR ExpressionAtlas; Q9NQX3; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB. DR GO; GO:0099572; C:postsynaptic specialization; IBA:GO_Central. DR GO; GO:0099634; C:postsynaptic specialization membrane; IEA:GOC. DR GO; GO:0097060; C:synaptic membrane; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061598; F:molybdopterin adenylyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0043546; F:molybdopterin cofactor binding; IDA:CAFA. DR GO; GO:0061599; F:molybdopterin molybdotransferase activity; IBA:GO_Central. DR GO; GO:0008940; F:nitrate reductase activity; IMP:CAFA. DR GO; GO:0007529; P:establishment of synaptic specificity at neuromuscular junction; IBA:GO_Central. DR GO; GO:0097112; P:gamma-aminobutyric acid receptor clustering; IDA:UniProtKB. DR GO; GO:0072579; P:glycine receptor clustering; IBA:GO_Central. DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IBA:GO_Central. DR GO; GO:0032324; P:molybdopterin cofactor biosynthetic process; IDA:UniProtKB. DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IBA:GO_Central. DR GO; GO:0010038; P:response to metal ion; IMP:CAFA. DR CDD; cd00887; MoeA; 1. DR CDD; cd00886; MogA_MoaB; 1. DR Gene3D; 3.40.980.10; MoaB/Mog-like domain; 2. DR Gene3D; 2.40.340.10; MoeA, C-terminal, domain IV; 1. DR Gene3D; 3.90.105.10; Molybdopterin biosynthesis moea protein, domain 2; 1. DR Gene3D; 2.170.190.11; Molybdopterin biosynthesis moea protein, domain 3; 1. DR InterPro; IPR036425; MoaB/Mog-like_dom_sf. DR InterPro; IPR001453; MoaB/Mog_dom. DR InterPro; IPR008284; MoCF_biosynth_CS. DR InterPro; IPR038987; MoeA-like. DR InterPro; IPR005111; MoeA_C_domain_IV. DR InterPro; IPR036688; MoeA_C_domain_IV_sf. DR InterPro; IPR005110; MoeA_linker/N. DR InterPro; IPR036135; MoeA_linker/N_sf. DR NCBIfam; TIGR00177; molyb_syn; 2. DR PANTHER; PTHR10192:SF5; GEPHYRIN; 1. DR PANTHER; PTHR10192; MOLYBDOPTERIN BIOSYNTHESIS PROTEIN; 1. DR Pfam; PF00994; MoCF_biosynth; 2. DR Pfam; PF03454; MoeA_C; 1. DR Pfam; PF03453; MoeA_N; 1. DR SMART; SM00852; MoCF_biosynth; 2. DR SUPFAM; SSF63867; MoeA C-terminal domain-like; 1. DR SUPFAM; SSF63882; MoeA N-terminal region -like; 1. DR SUPFAM; SSF53218; Molybdenum cofactor biosynthesis proteins; 2. DR PROSITE; PS01078; MOCF_BIOSYNTHESIS_1; 1. DR PROSITE; PS01079; MOCF_BIOSYNTHESIS_2; 1. DR Genevisible; Q9NQX3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Cell projection; Cytoplasm; Cytoskeleton; Disease variant; Lipoprotein; KW Magnesium; Membrane; Metal-binding; Molybdenum; KW Molybdenum cofactor biosynthesis; Multifunctional enzyme; KW Nucleotide-binding; Palmitate; Phosphoprotein; Postsynaptic cell membrane; KW Reference proteome; Synapse; Transferase. FT CHAIN 1..736 FT /note="Gephyrin" FT /id="PRO_0000170964" FT REGION 14..166 FT /note="MPT Mo-transferase" FT REGION 140..316 FT /note="Interaction with GABARAP" FT /evidence="ECO:0000250" FT REGION 181..232 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 260..290 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 326..736 FT /note="MPT adenylyltransferase" FT COMPBIAS 206..225 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 188 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569" FT MOD_RES 194 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569" FT MOD_RES 198 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 200 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BUV3" FT MOD_RES 262 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BUV3" FT MOD_RES 265 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8BUV3" FT MOD_RES 266 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:16964243" FT MOD_RES 268 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BUV3" FT MOD_RES 270 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BUV3" FT MOD_RES 305 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT LIPID 212 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:25025157" FT LIPID 284 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:25025157" FT VAR_SEQ 243 FT /note="K -> KKHPFYTSPAVVMAHGEQPIPGLINYSHHSTDER (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:11418245, FT ECO:0000303|PubMed:15489334" FT /id="VSP_021769" FT VARIANT 10 FT /note="N -> Y (found in a patient with hyperekplexia; FT uncertain significance; does not disrupt GLRB-GPHN FT interactions; does not affect the structural lattices FT formed by GPHN; dbSNP:rs121908539)" FT /evidence="ECO:0000269|PubMed:12684523" FT /id="VAR_044162" FT VARIANT 375 FT /note="G -> D (in MOCODC; patient phenotype resembling FT Dravet syndrome; abolishes postsynaptic clustering of GPHN; FT decreases cell-surface expression of GABA receptors; FT impairs postsynaptic currents; catalytically inactive; FT decreases binding affinity toward GABRA3; decreases binding FT affinity toward GLRB)" FT /evidence="ECO:0000269|PubMed:26613940" FT /id="VAR_075626" FT VARIANT 580 FT /note="D -> A (in MOCODC; lacks molybdenum cofactor FT synthesis activity; dbSNP:rs397518420)" FT /evidence="ECO:0000269|PubMed:22040219, FT ECO:0000269|PubMed:26613940" FT /id="VAR_070275" FT MUTAGEN 212 FT /note="C->S: Decreased palmitoylation. Decreased clustering FT at synaptic membranes. Decreased function in FT gamma-aminobutyric acid receptor clustering. Loss of FT palmitoylation, decreased clustering at synaptic membranes FT and loss of function in gamma-aminobutyric acid receptor FT clustering; when associated with S-284." FT /evidence="ECO:0000269|PubMed:25025157" FT MUTAGEN 284 FT /note="C->S: Decreased palmitoylation. Decreased clustering FT at synaptic membranes. Decreased function in FT gamma-aminobutyric acid receptor clustering. Loss of FT palmitoylation, decreased clustering at synaptic membranes FT and loss of function in gamma-aminobutyric acid receptor FT clustering; when associated with S-212." FT /evidence="ECO:0000269|PubMed:25025157" FT CONFLICT 261 FT /note="A -> V (in Ref. 1; CAC81240)" FT /evidence="ECO:0000305" FT STRAND 16..22 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 24..27 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 34..44 FT /evidence="ECO:0007829|PDB:1JLJ" FT TURN 46..49 FT /evidence="ECO:0007829|PDB:1JLJ" FT STRAND 52..59 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 63..75 FT /evidence="ECO:0007829|PDB:1JLJ" FT STRAND 80..86 FT /evidence="ECO:0007829|PDB:1JLJ" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 96..103 FT /evidence="ECO:0007829|PDB:1JLJ" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 109..122 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 124..128 FT /evidence="ECO:0007829|PDB:1JLJ" FT STRAND 133..136 FT /evidence="ECO:0007829|PDB:1JLJ" FT STRAND 139..144 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 148..158 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 162..169 FT /evidence="ECO:0007829|PDB:1JLJ" FT HELIX 175..178 FT /evidence="ECO:0007829|PDB:1JLJ" SQ SEQUENCE 736 AA; 79748 MW; E2BDA3AD3AB962C0 CRC64; MATEGMILTN HDHQIRVGVL TVSDSCFRNL AEDRSGINLK DLVQDPSLLG GTISAYKIVP DEIEEIKETL IDWCDEKELN LILTTGGTGF APRDVTPEAT KEVIEREAPG MALAMLMGSL NVTPLGMLSR PVCGIRGKTL IINLPGSKKG SQECFQFILP ALPHAIDLLR DAIVKVKEVH DELEDLPSPP PPLSPPPTTS PHKQTEDKGV QCEEEEEEKK DSGVASTEDS SSSHITAAAI AAKIPDSIIS RGVQVLPRDT ASLSTTPSES PRAQATSRLS TASCPTPKVQ SRCSSKENIL RASHSAVDIT KVARRHRMSP FPLTSMDKAF ITVLEMTPVL GTEIINYRDG MGRVLAQDVY AKDNLPPFPA SVKDGYAVRA ADGPGDRFII GESQAGEQPT QTVMPGQVMR VTTGAPIPCG ADAVVQVEDT ELIRESDDGT EELEVRILVQ ARPGQDIRPI GHDIKRGECV LAKGTHMGPS EIGLLATVGV TEVEVNKFPV VAVMSTGNEL LNPEDDLLPG KIRDSNRSTL LATIQEHGYP TINLGIVGDN PDDLLNALNE GISRADVIIT SGGVSMGEKD YLKQVLDIDL HAQIHFGRVF MKPGLPTTFA TLDIDGVRKI IFALPGNPVS AVVTCNLFVV PALRKMQGIL DPRPTIIKAR LSCDVKLDPR PEYHRCILTW HHQEPLPWAQ STGNQMSSRL MSMRSANGLL MLPPKTEQYV ELHKGEVVDV MVIGRL //