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Database: UniProt
Entry: Q03555
LinkDB: Q03555
Original site: Q03555 
ID   GEPH_RAT                Reviewed;         768 AA.
AC   Q03555;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   16-MAY-2006, sequence version 3.
DT   26-NOV-2014, entry version 150.
DE   RecName: Full=Gephyrin;
DE   AltName: Full=Putative glycine receptor-tubulin linker protein;
DE   Includes:
DE     RecName: Full=Molybdopterin adenylyltransferase;
DE              Short=MPT adenylyltransferase;
DE              EC=2.7.7.75;
DE     AltName: Full=Domain G;
DE   Includes:
DE     RecName: Full=Molybdopterin molybdenumtransferase;
DE              Short=MPT Mo-transferase;
DE              EC=2.10.1.1;
DE     AltName: Full=Domain E;
GN   Name=Gphn; Synonyms=Gph;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND PARTIAL PROTEIN SEQUENCE.
RC   STRAIN=Wistar; TISSUE=Brain;
RX   PubMed=1319186; DOI=10.1016/0896-6273(92)90136-2;
RA   Prior P., Schmitt B., Grenningloh G., Pribilla I., Multhaup G.,
RA   Beyreuther K., Maulet Y., Werner P., Langosch D., Kirsch J., Betz H.;
RT   "Primary structure and alternative splice variants of gephyrin, a
RT   putative glycine receptor-tubulin linker protein.";
RL   Neuron 8:1161-1170(1992).
RN   [2]
RP   SEQUENCE REVISION TO 255.
RA   Schmitt B.;
RL   Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
RX   PubMed=11083919; DOI=10.1006/mcne.2000.0899;
RA   Meier J., De Chaldee M., Triller A., Vannier C.;
RT   "Functional heterogeneity of gephyrins.";
RL   Mol. Cell. Neurosci. 16:566-577(2000).
RN   [4]
RP   PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, X-RAY
RP   CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 348-768 IN COMPLEX WITH GLRB, AND
RP   SUBUNIT.
RX   PubMed=15201864; DOI=10.1038/sj.emboj.7600256;
RA   Sola M., Bavro V.N., Timmins J., Franz T., Ricard-Blum S., Schoehn G.,
RA   Ruigrok R.W.H., Paarmann I., Saiyed T., O'Sullivan G.A., Schmitt B.,
RA   Betz H., Weissenhorn W.;
RT   "Structural basis of dynamic glycine receptor clustering by
RT   gephyrin.";
RL   EMBO J. 23:2510-2519(2004).
RN   [5]
RP   FUNCTION.
RX   PubMed=8264797; DOI=10.1038/366745a0;
RA   Kirsch J., Wolters I., Triller A., Betz H.;
RT   "Gephyrin antisense oligonucleotides prevent glycine receptor
RT   clustering in spinal neurons.";
RL   Nature 366:745-748(1993).
RN   [6]
RP   INTERACTION WITH GABARAP.
RX   PubMed=10900017; DOI=10.1073/pnas.97.15.8594;
RA   Kneussel M., Haverkamp S., Fuhrmann J.C., Wang H., Waessle H.,
RA   Olsen R.W., Betz H.;
RT   "The gamma-aminobutyric acid type A receptor (GABAAR)-associated
RT   protein GABARAP interacts with gephyrin but is not involved in
RT   receptor anchoring at the synapse.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:8594-8599(2000).
RN   [7]
RP   FUNCTION.
RX   PubMed=9990024; DOI=10.1073/pnas.96.4.1333;
RA   Stallmeyer B., Schwarz G., Schulze J., Nerlich A., Reiss J.,
RA   Kirsch J., Mendel R.R.;
RT   "The neurotransmitter receptor-anchoring protein gephyrin
RT   reconstitutes molybdenum cofactor biosynthesis in bacteria, plants,
RT   and mammalian cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1333-1338(1999).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-201, AND SUBUNIT.
RX   PubMed=11325967; DOI=10.1074/jbc.M101923200;
RA   Sola M., Kneussel M., Heck I.S., Betz H., Weissenhorn W.;
RT   "X-ray crystal structure of the trimeric N-terminal domain of
RT   gephyrin.";
RL   J. Biol. Chem. 276:25294-25301(2001).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 350-768 IN COMPLEX WITH GLRB,
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-362; PRO-745 AND
RP   745-PRO-PRO-746.
RX   PubMed=16511563; DOI=10.1038/sj.emboj.7601029;
RA   Kim E.Y., Schrader N., Smolinsky B., Bedet C., Vannier C., Schwarz G.,
RA   Schindelin H.;
RT   "Deciphering the structural framework of glycine receptor anchoring by
RT   gephyrin.";
RL   EMBO J. 25:1385-1395(2006).
CC   -!- FUNCTION: Microtubule-associated protein involved in membrane
CC       protein-cytoskeleton interactions. It is thought to anchor the
CC       inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By
CC       similarity). Catalyzes two steps in the biosynthesis of the
CC       molybdenum cofactor. In the first step, molybdopterin is
CC       adenylated. Subsequently, molybdate is inserted into adenylated
CC       molybdopterin and AMP is released. {ECO:0000250,
CC       ECO:0000269|PubMed:8264797, ECO:0000269|PubMed:9990024}.
CC   -!- CATALYTIC ACTIVITY: ATP + molybdopterin = diphosphate + adenylyl-
CC       molybdopterin.
CC   -!- CATALYTIC ACTIVITY: Adenylyl-molybdopterin + molybdate =
CC       molybdenum cofactor + AMP.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- ENZYME REGULATION: Inhibited by copper and tungsten.
CC       {ECO:0000250}.
CC   -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
CC   -!- SUBUNIT: Homotrimer, homodimer and homooligomer. Interacts with
CC       SRGAP2 (via SH3 domain) (By similarity). Interacts with GLRB and
CC       GABARAP. {ECO:0000250, ECO:0000269|PubMed:10900017,
CC       ECO:0000269|PubMed:11325967, ECO:0000269|PubMed:15201864,
CC       ECO:0000269|PubMed:16511563}.
CC   -!- INTERACTION:
CC       P20236:Gabra3; NbExp=5; IntAct=EBI-5273276, EBI-5273284;
CC       P48168:Glrb (xeno); NbExp=4; IntAct=EBI-349317, EBI-7069198;
CC   -!- SUBCELLULAR LOCATION: Cell junction, synapse
CC       {ECO:0000269|PubMed:16511563}. Cell junction, synapse,
CC       postsynaptic cell membrane {ECO:0000269|PubMed:16511563};
CC       Peripheral membrane protein {ECO:0000269|PubMed:16511563};
CC       Cytoplasmic side {ECO:0000269|PubMed:16511563}. Cytoplasm,
CC       cytoskeleton {ECO:0000269|PubMed:16511563}. Note=Cytoplasmic face
CC       of glycinergic postsynaptic membranes.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=6;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=6;
CC         IsoId=Q03555-1; Sequence=Displayed;
CC       Name=1; Synonyms=GE124'56;
CC         IsoId=Q03555-2; Sequence=VSP_003238;
CC       Name=2; Synonyms=GE236;
CC         IsoId=Q03555-3; Sequence=VSP_003239, VSP_003240, VSP_003243;
CC       Name=3; Synonyms=GE24'6;
CC         IsoId=Q03555-4; Sequence=VSP_003239;
CC       Name=4; Synonyms=GE245;
CC         IsoId=Q03555-5; Sequence=VSP_003241, VSP_003242;
CC       Name=5; Synonyms=GE26;
CC         IsoId=Q03555-6; Sequence=VSP_003239, VSP_003243;
CC   -!- TISSUE SPECIFICITY: Expressed in tissues including spinal cord,
CC       brain, liver, kidney and lung.
CC   -!- PTM: Phosphorylated.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the MoaB/Mog
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the MoeA family.
CC       {ECO:0000305}.
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DR   EMBL; X66366; CAA47009.2; -; mRNA.
DR   PIR; JH0681; JH0681.
DR   RefSeq; NP_074056.2; NM_022865.3. [Q03555-6]
DR   UniGene; Rn.11032; -.
DR   PDB; 1IHC; X-ray; 1.90 A; A=1-201.
DR   PDB; 1T3E; X-ray; 3.25 A; A/B=348-768.
DR   PDB; 2FTS; X-ray; 2.41 A; A=350-768.
DR   PDB; 2FU3; X-ray; 2.70 A; A/B=350-768.
DR   PDB; 4PD0; X-ray; 1.70 A; A=350-768.
DR   PDB; 4PD1; X-ray; 1.98 A; A=350-768.
DR   PDBsum; 1IHC; -.
DR   PDBsum; 1T3E; -.
DR   PDBsum; 2FTS; -.
DR   PDBsum; 2FU3; -.
DR   PDBsum; 4PD0; -.
DR   PDBsum; 4PD1; -.
DR   ProteinModelPortal; Q03555; -.
DR   SMR; Q03555; 13-194, 350-768.
DR   BioGrid; 249211; 8.
DR   DIP; DIP-33263N; -.
DR   IntAct; Q03555; 5.
DR   MINT; MINT-241818; -.
DR   PhosphoSite; Q03555; -.
DR   PaxDb; Q03555; -.
DR   PRIDE; Q03555; -.
DR   GeneID; 64845; -.
DR   KEGG; rno:64845; -.
DR   UCSC; RGD:69194; rat. [Q03555-1]
DR   CTD; 10243; -.
DR   RGD; 69194; Gphn.
DR   eggNOG; COG0303; -.
DR   HOGENOM; HOG000280651; -.
DR   HOVERGEN; HBG005828; -.
DR   InParanoid; Q03555; -.
DR   KO; K15376; -.
DR   PhylomeDB; Q03555; -.
DR   UniPathway; UPA00344; -.
DR   EvolutionaryTrace; Q03555; -.
DR   NextBio; 613764; -.
DR   PRO; PR:Q03555; -.
DR   Genevestigator; Q03555; -.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR   GO; GO:0060077; C:inhibitory synapse; IDA:BHF-UCL.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
DR   GO; GO:0045202; C:synapse; IDA:RGD.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0061598; F:molybdopterin adenylyltransferase activity; IDA:MGI.
DR   GO; GO:0061599; F:molybdopterin molybdotransferase activity; IDA:MGI.
DR   GO; GO:0030674; F:protein binding, bridging; TAS:RGD.
DR   GO; GO:0032947; F:protein complex scaffold; IDA:RGD.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:RGD.
DR   GO; GO:0005102; F:receptor binding; IPI:RGD.
DR   GO; GO:0015631; F:tubulin binding; TAS:RGD.
DR   GO; GO:0045184; P:establishment of protein localization; IMP:BHF-UCL.
DR   GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IDA:MGI.
DR   GO; GO:0051260; P:protein homooligomerization; IDA:RGD.
DR   GO; GO:0006605; P:protein targeting; TAS:RGD.
DR   GO; GO:0007416; P:synapse assembly; IEP:RGD.
DR   Gene3D; 2.40.340.10; -; 1.
DR   Gene3D; 3.40.980.10; -; 2.
DR   InterPro; IPR020817; Mo_cofactor_synthesis.
DR   InterPro; IPR008284; MoCF_biosynth_CS.
DR   InterPro; IPR005111; MoeA_C_domain_IV.
DR   InterPro; IPR005110; MoeA_linker/N.
DR   InterPro; IPR001453; Mopterin-bd_dom.
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 junction;
KW   Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW   Direct protein sequencing; Magnesium; Membrane; Metal-binding;
KW   Molybdenum; Molybdenum cofactor biosynthesis; Multifunctional enzyme;
KW   Nucleotide-binding; Phosphoprotein; Postsynaptic cell membrane;
KW   Reference proteome; Synapse; Transferase.
FT   CHAIN         1    768       Gephyrin.
FT                                /FTId=PRO_0000170965.
FT   REGION       14    166       MPT Mo-transferase.
FT   REGION      153    348       Interaction with GABARAP.
FT   REGION      326    768       MPT adenylyltransferase.
FT   COMPBIAS    213    218       Glu-rich (acidic).
FT   MOD_RES     201    201       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     207    207       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     279    279       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES     337    337       Phosphoserine. {ECO:0000250}.
FT   VAR_SEQ       1     22       MATEGMILTNHDHQIRVGVLTV -> MSFPLSPAFTLLHIL
FT                                V (in isoform 1).
FT                                {ECO:0000303|PubMed:11083919}.
FT                                /FTId=VSP_003238.
FT   VAR_SEQ      99    111       Missing (in isoform 5, isoform 2 and
FT                                isoform 3). {ECO:0000303|PubMed:11083919,
FT                                ECO:0000303|PubMed:1319186}.
FT                                /FTId=VSP_003239.
FT   VAR_SEQ     256    256       K -> KNHPFYTSPAVFMANHGQPIPGLISYSHHATGSADK
FT                                R (in isoform 2).
FT                                {ECO:0000303|PubMed:11083919}.
FT                                /FTId=VSP_003240.
FT   VAR_SEQ     302    320       Missing (in isoform 5 and isoform 2).
FT                                {ECO:0000303|PubMed:11083919,
FT                                ECO:0000303|PubMed:1319186}.
FT                                /FTId=VSP_003243.
FT   VAR_SEQ     302    315       QIRRPDESKGVASR -> ARLPSCSSTYSVSE (in
FT                                isoform 4).
FT                                {ECO:0000303|PubMed:11083919}.
FT                                /FTId=VSP_003241.
FT   VAR_SEQ     316    320       Missing (in isoform 4).
FT                                {ECO:0000303|PubMed:11083919}.
FT                                /FTId=VSP_003242.
FT   MUTAGEN     362    362       F->A: Reduced GLRB binding.
FT                                {ECO:0000269|PubMed:16511563}.
FT   MUTAGEN     745    746       PP->AA: Reduced GLRB binding.
FT                                {ECO:0000269|PubMed:16511563}.
FT   MUTAGEN     745    745       P->A: Loss of GLRB binding.
FT                                {ECO:0000269|PubMed:16511563}.
FT   CONFLICT    255    255       A -> R (in Ref. 3). {ECO:0000305}.
FT   STRAND       16     22       {ECO:0000244|PDB:1IHC}.
FT   HELIX        24     27       {ECO:0000244|PDB:1IHC}.
FT   HELIX        34     44       {ECO:0000244|PDB:1IHC}.
FT   TURN         46     49       {ECO:0000244|PDB:1IHC}.
FT   STRAND       52     59       {ECO:0000244|PDB:1IHC}.
FT   HELIX        63     75       {ECO:0000244|PDB:1IHC}.
FT   STRAND       80     86       {ECO:0000244|PDB:1IHC}.
FT   STRAND       89     91       {ECO:0000244|PDB:1IHC}.
FT   HELIX       112    116       {ECO:0000244|PDB:1IHC}.
FT   STRAND      118    120       {ECO:0000244|PDB:1IHC}.
FT   HELIX       122    135       {ECO:0000244|PDB:1IHC}.
FT   HELIX       137    141       {ECO:0000244|PDB:1IHC}.
FT   STRAND      146    149       {ECO:0000244|PDB:1IHC}.
FT   STRAND      152    157       {ECO:0000244|PDB:1IHC}.
FT   HELIX       161    171       {ECO:0000244|PDB:1IHC}.
FT   HELIX       172    174       {ECO:0000244|PDB:1IHC}.
FT   HELIX       175    182       {ECO:0000244|PDB:1IHC}.
FT   HELIX       188    193       {ECO:0000244|PDB:1IHC}.
FT   STRAND      355    357       {ECO:0000244|PDB:2FTS}.
FT   HELIX       358    368       {ECO:0000244|PDB:4PD0}.
FT   STRAND      374    378       {ECO:0000244|PDB:4PD0}.
FT   HELIX       379    381       {ECO:0000244|PDB:4PD0}.
FT   STRAND      386    389       {ECO:0000244|PDB:4PD0}.
FT   STRAND      397    400       {ECO:0000244|PDB:4PD0}.
FT   STRAND      402    410       {ECO:0000244|PDB:4PD0}.
FT   HELIX       412    414       {ECO:0000244|PDB:4PD0}.
FT   STRAND      416    425       {ECO:0000244|PDB:4PD0}.
FT   STRAND      439    443       {ECO:0000244|PDB:4PD0}.
FT   STRAND      455    458       {ECO:0000244|PDB:4PD0}.
FT   HELIX       459    461       {ECO:0000244|PDB:4PD0}.
FT   STRAND      462    467       {ECO:0000244|PDB:4PD0}.
FT   STRAND      469    472       {ECO:0000244|PDB:1T3E}.
FT   STRAND      473    479       {ECO:0000244|PDB:4PD0}.
FT   TURN        485    488       {ECO:0000244|PDB:4PD0}.
FT   STRAND      494    496       {ECO:0000244|PDB:4PD0}.
FT   STRAND      501    503       {ECO:0000244|PDB:4PD0}.
FT   HELIX       511    520       {ECO:0000244|PDB:4PD0}.
FT   STRAND      524    528       {ECO:0000244|PDB:4PD0}.
FT   STRAND      533    538       {ECO:0000244|PDB:4PD0}.
FT   HELIX       558    568       {ECO:0000244|PDB:4PD0}.
FT   STRAND      573    579       {ECO:0000244|PDB:4PD0}.
FT   HELIX       583    596       {ECO:0000244|PDB:4PD0}.
FT   STRAND      598    605       {ECO:0000244|PDB:4PD0}.
FT   STRAND      607    610       {ECO:0000244|PDB:4PD0}.
FT   HELIX       613    620       {ECO:0000244|PDB:4PD0}.
FT   STRAND      625    632       {ECO:0000244|PDB:4PD0}.
FT   STRAND      640    646       {ECO:0000244|PDB:4PD0}.
FT   STRAND      649    656       {ECO:0000244|PDB:4PD0}.
FT   HELIX       660    669       {ECO:0000244|PDB:4PD0}.
FT   HELIX       671    678       {ECO:0000244|PDB:4PD0}.
FT   STRAND      688    695       {ECO:0000244|PDB:4PD0}.
FT   STRAND      704    711       {ECO:0000244|PDB:4PD0}.
FT   STRAND      716    718       {ECO:0000244|PDB:1T3E}.
FT   STRAND      720    723       {ECO:0000244|PDB:4PD0}.
FT   STRAND      728    730       {ECO:0000244|PDB:2FTS}.
FT   HELIX       731    735       {ECO:0000244|PDB:4PD0}.
FT   STRAND      740    744       {ECO:0000244|PDB:4PD0}.
FT   STRAND      752    754       {ECO:0000244|PDB:4PD1}.
FT   STRAND      759    764       {ECO:0000244|PDB:4PD0}.
SQ   SEQUENCE   768 AA;  83266 MW;  FAD1B6DD76ED79EA CRC64;
     MATEGMILTN HDHQIRVGVL TVSDSCFRNL AEDRSGINLK DLVQDPSLLG GTISAYKIVP
     DEIEEIKETL IDWCDEKELN LILTTGGTGF APRDVTPEKF PTFPFCGLQK GATKEVIERE
     APGMALAMLM GSLNVTPLGM LSRPVCGIRG KTLIINLPGS KKGSQECFQF ILPALPHAID
     LLRDAIVKVK EVHDELEDLP SPPPPLSPPP TTSPHKQTED KGVQCEEEEE EKKDSGVAST
     EDSSSSHITA AALAAKIPDS IISRGVQVLP RDTASLSTTP SESPRAQATS RLSTASCPTP
     KQIRRPDESK GVASRVGSLK VQSRCSSKEN ILRASHSAVD ITKVARRHRM SPFPLTSMDK
     AFITVLEMTP VLGTEIINYR DGMGRVLAQD VYAKDNLPPF PASVKDGYAV RAADGPGDRF
     IIGESQAGEQ PTQTVMPGQV MRVTTGAPIP CGADAVVQVE DTELIRESDD GTEELEVRIL
     VQARPGQDIR PIGHDIKRGE CVLAKGTHMG PSEIGLLATV GVTEVEVNKF PVVAVMSTGN
     ELLNPEDDLL PGKIRDSNRS TLLATIQEHG YPTINLGIVG DNPDDLLNAL NEGISRADVI
     ITSGGVSMGE KDYLKQVLDI DLHAQIHFGR VFMKPGLPTT FATLDIDGVR KIIFALPGNP
     VSAVVTCNLF VVPALRKMQG ILDPRPTIIK ARLSCDVKLD PRPEYHRCIL TWHHQEPLPW
     AQSTGNQMSS RLMSMRSANG LLMLPPKTEQ YVELHKGEVV DVMVIGRL
//
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