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 29-MAY-2013, entry version 136.
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, MASS SPECTROMETRY, X-RAY CRYSTALLOGRAPHY
RP (3.25 ANGSTROMS) OF 348-768 IN COMPLEX WITH GLRB, AND 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 -!- 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.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X66366; CAA47009.2; -; mRNA.
DR IPI; IPI00211800; -.
DR IPI; IPI00230795; -.
DR IPI; IPI00230796; -.
DR IPI; IPI00230797; -.
DR IPI; IPI00230798; -.
DR IPI; IPI00323990; -.
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 DIP; DIP-33263N; -.
DR IntAct; Q03555; 3.
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.
DR CTD; 10243; -.
DR RGD; 69194; Gphn.
DR eggNOG; COG0303; -.
DR HOGENOM; HOG000280651; -.
DR HOVERGEN; HBG005828; -.
DR InParanoid; Q03555; -.
DR KO; K15376; -.
DR UniPathway; UPA00344; -.
DR EvolutionaryTrace; Q03555; -.
DR NextBio; 613764; -.
DR ArrayExpress; Q03555; -.
DR Genevestigator; Q03555; -.
DR GermOnline; ENSRNOG00000028366; Rattus norvegicus.
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:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0015631; F:tubulin binding; TAS:RGD.
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; MoCF_biosynth; 2.
DR SUPFAM; SSF63867; MoeA_C; 1.
DR SUPFAM; SSF63882; MoeA_N; 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
//
