Gephyrin

NameGephyrin
Synonyms
  • GPH
  • KIAA1385
Gene NameGPHN
OrganismHuman
Amino acid sequence
>lcl|BSEQ0005202|Gephyrin
MATEGMILTNHDHQIRVGVLTVSDSCFRNLAEDRSGINLKDLVQDPSLLGGTISAYKIVP
DEIEEIKETLIDWCDEKELNLILTTGGTGFAPRDVTPEATKEVIEREAPGMALAMLMGSL
NVTPLGMLSRPVCGIRGKTLIINLPGSKKGSQECFQFILPALPHAIDLLRDAIVKVKEVH
DELEDLPSPPPPLSPPPTTSPHKQTEDKGVQCEEEEEEKKDSGVASTEDSSSSHITAAAI
AAKIPDSIISRGVQVLPRDTASLSTTPSESPRAQATSRLSTASCPTPKVQSRCSSKENIL
RASHSAVDITKVARRHRMSPFPLTSMDKAFITVLEMTPVLGTEIINYRDGMGRVLAQDVY
AKDNLPPFPASVKDGYAVRAADGPGDRFIIGESQAGEQPTQTVMPGQVMRVTTGAPIPCG
ADAVVQVEDTELIRESDDGTEELEVRILVQARPGQDIRPIGHDIKRGECVLAKGTHMGPS
EIGLLATVGVTEVEVNKFPVVAVMSTGNELLNPEDDLLPGKIRDSNRSTLLATIQEHGYP
TINLGIVGDNPDDLLNALNEGISRADVIITSGGVSMGEKDYLKQVLDIDLHAQIHFGRVF
MKPGLPTTFATLDIDGVRKIIFALPGNPVSAVVTCNLFVVPALRKMQGILDPRPTIIKAR
LSCDVKLDPRPEYHRCILTWHHQEPLPWAQSTGNQMSSRLMSMRSANGLLMLPPKTEQYV
ELHKGEVVDVMVIGRL
Number of residues736
Molecular Weight79747.635
Theoretical pI5.09
GO Classification
Functions
  • metal ion binding
  • molybdopterin adenylyltransferase activity
  • molybdopterin molybdotransferase activity
  • ATP binding
Processes
  • small molecule metabolic process
  • vitamin metabolic process
  • water-soluble vitamin metabolic process
  • Mo-molybdopterin cofactor biosynthetic process
  • molybdopterin cofactor biosynthetic process
  • establishment of synaptic specificity at neuromuscular junction
  • glycine receptor clustering
  • molybdenum incorporation into molybdenum-molybdopterin complex
Components
  • plasma membrane
  • cell junction
  • cytoplasm
  • cytoskeleton
  • postsynaptic membrane
General FunctionMolybdopterin molybdotransferase activity
Specific FunctionMicrotubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ9NQX3
UniProtKB Entry NameGEPH_HUMAN
Cellular LocationCell junction
Gene sequence
>lcl|BSEQ0021679|Gephyrin (GPHN)
ATGGCGACCGAGGGAATGATCCTTACTAACCACGACCATCAAATCCGTGTCGGAGTCCTT
ACAGTGAGTGATAGTTGCTTCAGGAATCTTGCAGAAGACCGCAGTGGGATAAATCTCAAA
GATCTCGTACAAGATCCTTCTTTGTTGGGTGGGACTATATCAGCATACAAGATAGTACCA
GATGAAATAGAAGAAATCAAGGAAACCCTGATAGATTGGTGTGATGAAAAGGAACTTAAT
TTGATATTAACAACTGGAGGAACAGGATTTGCACCACGAGATGTCACTCCAGAGGCCACA
AAAGAAGTAATAGAACGGGAAGCACCAGGGATGGCCCTGGCAATGCTGATGGGATCACTT
AATGTTACACCTCTGGGCATGCTCTCTAGGCCTGTATGTGGAATCAGAGGGAAAACGCTC
ATAATTAACCTGCCAGGTAGCAAGAAAGGATCTCAGGAATGCTTTCAATTCATACTGCCA
GCTCTACCTCATGCCATTGACCTTTTACGTGATGCCATTGTAAAAGTAAAGGAGGTGCAT
GATGAACTTGAAGATTTGCCTTCCCCACCTCCCCCTCTTTCCCCTCCTCCTACTACCAGC
CCCCATAAACAGACAGAAGACAAAGGAGTTCAATGTGAGGAAGAGGAAGAAGAGAAGAAA
GACAGTGGTGTTGCTTCAACAGAAGATAGTTCCTCATCACATATAACTGCAGCAGCCATT
GCTGCCAAGATTCCAGACTCCATCATTTCTCGTGGTGTTCAGGTGCTCCCACGAGACACA
GCCTCCCTCAGCACTACTCCTTCAGAATCGCCTCGTGCTCAGGCTACATCTCGCCTCTCT
ACAGCTTCCTGCCCAACACCAAAAGTCCAGTCCAGGTGCAGCAGCAAGGAGAACATTCTC
AGAGCCAGTCACAGTGCTGTCGATATCACCAAGGTGGCTAGAAGACATCGCATGTCTCCT
TTTCCTCTGACATCTATGGACAAAGCCTTTATCACAGTCCTGGAGATGACTCCGGTGCTT
GGGACAGAAATCATCAATTACCGAGATGGAATGGGGCGAGTCCTTGCTCAAGATGTATAT
GCAAAAGACAATTTACCCCCCTTCCCAGCATCAGTAAAAGATGGCTATGCTGTCCGAGCT
GCTGATGGCCCAGGAGATCGTTTCATCATTGGGGAATCCCAAGCTGGTGAACAGCCAACT
CAGACAGTAATGCCAGGACAAGTCATGCGGGTTACAACAGGTGCTCCAATACCCTGCGGT
GCTGATGCAGTAGTACAAGTGGAAGATACCGAACTTATCAGGGAATCAGATGATGGCACT
GAAGAACTTGAAGTGCGAATTCTGGTGCAAGCTCGGCCAGGCCAAGATATCAGACCCATC
GGCCATGACATTAAAAGAGGGGAATGTGTTTTGGCCAAAGGAACCCACATGGGCCCCTCA
GAGATTGGTCTTCTGGCAACTGTAGGTGTCACAGAGGTTGAAGTTAATAAGTTTCCAGTG
GTTGCAGTCATGTCAACAGGGAATGAGCTGCTAAATCCTGAAGATGACCTCTTACCAGGG
AAGATTCGAGACAGCAATCGTTCAACTCTTCTAGCAACAATTCAGGAACATGGTTACCCC
ACGATCAACTTGGGTATTGTAGGAGACAACCCAGATGACTTACTCAATGCCTTGAATGAG
GGTATCAGTCGTGCTGATGTCATCATCACATCAGGGGGTGTATCCATGGGGGAAAAGGAC
TATCTCAAGCAGGTGCTGGACATTGATCTTCATGCTCAGATCCATTTTGGCAGGGTTTTT
ATGAAACCAGGCTTGCCAACAACATTTGCAACTTTGGATATTGATGGTGTAAGAAAAATA
ATCTTTGCACTACCTGGGAATCCTGTATCGGCTGTGGTCACCTGCAATCTCTTTGTTGTG
CCTGCACTGAGGAAAATGCAGGGCATCTTGGATCCTCGGCCAACCATCATCAAAGCAAGG
TTATCATGTGATGTAAAACTTGATCCTCGTCCAGAATACCATCGGTGTATACTAACTTGG
CATCACCAAGAACCACTACCTTGGGCACAGAGTACAGGTAATCAAATGAGCAGCCGTCTG
ATGAGCATGCGCAGTGCCAATGGATTGTTGATGCTACCTCCAAAGACAGAACAGTACGTG
GAGCTCCACAAAGGCGAGGTGGTGGATGTCATGGTCATTGGACGGCTATGA
GenBank Gene IDAF272663
GeneCard IDNot Available
GenAtlas IDGPHN
HGNC IDHGNC:15465
Chromosome Location14
Locus14q23.3
References
  1. Reiss J, Gross-Hardt S, Christensen E, Schmidt P, Mendel RR, Schwarz G: A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency. Am J Hum Genet. 2001 Jan;68(1):208-13. Epub 2000 Nov 28. 11095995
  2. David-Watine B: The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells. Gene. 2001 Jun 27;271(2):239-45. 11418245
  3. Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O: Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Feb 28;7(1):65-73. 10718198
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  5. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. 16964243
  6. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  7. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  8. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  9. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  10. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  12. Schwarz G, Schrader N, Mendel RR, Hecht HJ, Schindelin H: Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications. J Mol Biol. 2001 Sep 14;312(2):405-18. 11554796
  13. Rees MI, Harvey K, Ward H, White JH, Evans L, Duguid IC, Hsu CC, Coleman SL, Miller J, Baer K, Waldvogel HJ, Gibbon F, Smart TG, Owen MJ, Harvey RJ, Snell RG: Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia. J Biol Chem. 2003 Jul 4;278(27):24688-96. Epub 2003 Apr 8. 12684523
  14. Reiss J, Lenz U, Aquaviva-Bourdain C, Joriot-Chekaf S, Mention-Mulliez K, Holder-Espinasse M: A GPHN point mutation leading to molybdenum cofactor deficiency. Clin Genet. 2011 Dec;80(6):598-9. doi: 10.1111/j.1399-0004.2011.01709.x. 22040219