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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   16-APR-2014, entry version 145.
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.
CC   -!- CATALYTIC ACTIVITY: ATP + molybdopterin = diphosphate + adenylyl-
CC       molybdopterin.
CC   -!- CATALYTIC ACTIVITY: Adenylyl-molybdopterin + molybdate =
CC       molybdenum cofactor + AMP.
CC   -!- COFACTOR: Magnesium.
CC   -!- ENZYME REGULATION: Inhibited by copper and tungsten (By
CC       similarity).
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.
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. Cell junction,
CC       synapse, postsynaptic cell membrane; Peripheral membrane protein;
CC       Cytoplasmic side. Cytoplasm, cytoskeleton. 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.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the MoeA family.
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DR   EMBL; X66366; CAA47009.2; -; mRNA.
DR   PIR; JH0681; JH0681.
DR   RefSeq; NP_074056.2; NM_022865.3.
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   PDBsum; 1IHC; -.
DR   PDBsum; 1T3E; -.
DR   PDBsum; 2FTS; -.
DR   PDBsum; 2FU3; -.
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-SubCell.
DR   GO; GO:0060077; C:inhibitory synapse; IDA:BHF-UCL.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR   GO; GO:0061599; F:molybdopterin molybdotransferase activity; IEA:UniProtKB-EC.
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; IEA:UniProtKB-KW.
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 (By similarity).
FT   MOD_RES     207    207       Phosphoserine (By similarity).
FT   MOD_RES     279    279       Phosphothreonine (By similarity).
FT   MOD_RES     337    337       Phosphoserine (By similarity).
FT   VAR_SEQ       1     22       MATEGMILTNHDHQIRVGVLTV -> MSFPLSPAFTLLHIL
FT                                V (in isoform 1).
FT                                /FTId=VSP_003238.
FT   VAR_SEQ      99    111       Missing (in isoform 5, isoform 2 and
FT                                isoform 3).
FT                                /FTId=VSP_003239.
FT   VAR_SEQ     256    256       K -> KNHPFYTSPAVFMANHGQPIPGLISYSHHATGSADK
FT                                R (in isoform 2).
FT                                /FTId=VSP_003240.
FT   VAR_SEQ     302    320       Missing (in isoform 5 and isoform 2).
FT                                /FTId=VSP_003243.
FT   VAR_SEQ     302    315       QIRRPDESKGVASR -> ARLPSCSSTYSVSE (in
FT                                isoform 4).
FT                                /FTId=VSP_003241.
FT   VAR_SEQ     316    320       Missing (in isoform 4).
FT                                /FTId=VSP_003242.
FT   MUTAGEN     362    362       F->A: Reduced GLRB binding.
FT   MUTAGEN     745    746       PP->AA: Reduced GLRB binding.
FT   MUTAGEN     745    745       P->A: Loss of GLRB binding.
FT   CONFLICT    255    255       A -> R (in Ref. 3).
FT   STRAND       16     22
FT   HELIX        24     27
FT   HELIX        34     44
FT   TURN         46     49
FT   STRAND       52     59
FT   HELIX        63     75
FT   STRAND       80     86
FT   STRAND       89     91
FT   HELIX       112    116
FT   STRAND      118    120
FT   HELIX       122    135
FT   HELIX       137    141
FT   STRAND      146    149
FT   STRAND      152    157
FT   HELIX       161    171
FT   HELIX       172    174
FT   HELIX       175    182
FT   HELIX       188    193
FT   STRAND      355    357
FT   HELIX       358    368
FT   STRAND      374    378
FT   HELIX       379    381
FT   STRAND      386    389
FT   STRAND      397    400
FT   STRAND      402    410
FT   HELIX       412    414
FT   STRAND      418    424
FT   STRAND      439    443
FT   STRAND      455    458
FT   HELIX       459    461
FT   STRAND      462    468
FT   STRAND      469    472
FT   STRAND      474    479
FT   TURN        485    488
FT   STRAND      494    496
FT   STRAND      501    503
FT   HELIX       511    520
FT   STRAND      524    528
FT   STRAND      533    538
FT   HELIX       558    567
FT   TURN        568    570
FT   STRAND      573    579
FT   HELIX       583    596
FT   STRAND      598    604
FT   STRAND      607    609
FT   HELIX       612    619
FT   TURN        620    622
FT   STRAND      625    632
FT   STRAND      640    646
FT   STRAND      649    656
FT   HELIX       660    678
FT   STRAND      688    695
FT   STRAND      704    711
FT   STRAND      716    718
FT   STRAND      720    723
FT   STRAND      728    730
FT   STRAND      740    744
FT   STRAND      752    754
FT   STRAND      759    764
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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