GEPH_HUMAN
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 03-AUG-2022, entry version 197.
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="http://atlasgeneticsoncology.org/Genes/GPHNID317.html";
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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; 65.
DR DIP; DIP-41076N; -.
DR IntAct; Q9NQX3; 24.
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 GlyGen; Q9NQX3; 2 sites, 1 O-linked glycan (2 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; Q9NQX3; -.
DR PeptideAtlas; Q9NQX3; -.
DR PRIDE; Q9NQX3; -.
DR ProteomicsDB; 82221; -. [Q9NQX3-1]
DR ProteomicsDB; 82222; -. [Q9NQX3-2]
DR ABCD; Q9NQX3; 9 sequenced antibodies.
DR Antibodypedia; 144; 416 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 CTD; 10243; -.
DR DisGeNET; 10243; -.
DR GeneCards; GPHN; -.
DR GeneReviews; GPHN; -.
DR HGNC; HGNC:15465; GPHN.
DR HPA; ENSG00000171723; Tissue enhanced (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; RHRESPY; -.
DR OrthoDB; 1114121at2759; -.
DR PhylomeDB; Q9NQX3; -.
DR TreeFam; TF300902; -.
DR BioCyc; MetaCyc:ENSG00000171723-MON; -.
DR PathwayCommons; Q9NQX3; -.
DR Reactome; R-HSA-947581; Molybdenum cofactor biosynthesis.
DR SignaLink; Q9NQX3; -.
DR SIGNOR; Q9NQX3; -.
DR UniPathway; UPA00344; -.
DR BioGRID-ORCS; 10243; 8 hits in 1075 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 176 other tissues.
DR ExpressionAtlas; Q9NQX3; baseline and differential.
DR Genevisible; Q9NQX3; HS.
DR GO; GO:0099144; C:anchored component of synaptic membrane; ISS:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0018315; P:molybdenum incorporation into molybdenum-molybdopterin complex; 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; 2.40.340.10; -; 1.
DR Gene3D; 3.40.980.10; -; 2.
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 PANTHER; PTHR10192; PTHR10192; 2.
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; SSF53218; SSF53218; 2.
DR SUPFAM; SSF63867; SSF63867; 1.
DR SUPFAM; SSF63882; SSF63882; 1.
DR TIGRFAMs; TIGR00177; molyb_syn; 2.
DR PROSITE; PS01078; MOCF_BIOSYNTHESIS_1; 1.
DR PROSITE; PS01079; MOCF_BIOSYNTHESIS_2; 1.
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 unknown pathological significance; does not disrupt GLRB-
FT GPHN 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 gamma-
FT 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 gamma-
FT 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
