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Q03555 (GEPH_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gephyrin
Alternative name(s):
Putative glycine receptor-tubulin linker protein

Including the following 2 domains:

  1. Molybdopterin adenylyltransferase
    Short name=MPT adenylyltransferase
    EC=2.7.7.75
    Alternative name(s):
    Domain G
  2. Molybdopterin molybdenumtransferase
    Short name=MPT Mo-transferase
    EC=2.10.1.1
    Alternative name(s):
    Domain E
Gene names
Name:Gphn
Synonyms:Gph
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length768 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Microtubule-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. Ref.5 Ref.7

Catalytic activity

ATP + molybdopterin = diphosphate + adenylyl-molybdopterin.

Adenylyl-molybdopterin + molybdate = molybdenum cofactor + AMP.

Cofactor

Magnesium.

Enzyme regulation

Inhibited by copper and tungsten By similarity.

Pathway

Cofactor biosynthesis; molybdopterin biosynthesis.

Subunit structure

Homotrimer, homodimer and homooligomer. Interacts with SRGAP2 (via SH3 domain) By similarity. Interacts with GLRB and GABARAP. Ref.4 Ref.6 Ref.8

Subcellular location

Cell junctionsynapse. Cell junctionsynapsepostsynaptic cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmcytoskeleton. Note: Cytoplasmic face of glycinergic postsynaptic membranes. Ref.9

Tissue specificity

Expressed in tissues including spinal cord, brain, liver, kidney and lung.

Post-translational modification

Phosphorylated.

Sequence similarities

In the N-terminal section; belongs to the MoaB/Mog family.

In the C-terminal section; belongs to the MoeA family.

Ontologies

Keywords
   Biological processMolybdenum cofactor biosynthesis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoskeleton
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Molybdenum
Nucleotide-binding
   Molecular functionTransferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processMo-molybdopterin cofactor biosynthetic process

Inferred from direct assay PubMed 23163752. Source: MGI

establishment of protein localization

Inferred from mutant phenotype PubMed 19914352. Source: BHF-UCL

protein homooligomerization

Inferred from direct assay PubMed 14976213. Source: RGD

protein targeting

Traceable author statement PubMed 11095995. Source: RGD

synapse assembly

Inferred from expression pattern PubMed 9130666. Source: RGD

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay PubMed 12967995. Source: RGD

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

inhibitory synapse

Inferred from direct assay PubMed 18550748. Source: BHF-UCL

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

synapse

Inferred from direct assay PubMed 12967995. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

molybdopterin adenylyltransferase activity

Inferred from direct assay PubMed 23163752. Source: MGI

molybdopterin molybdotransferase activity

Inferred from direct assay PubMed 23163752. Source: MGI

protein binding

Inferred from physical interaction PubMed 15215304. Source: UniProtKB

protein binding, bridging

Traceable author statement Ref.1. Source: RGD

protein complex scaffold

Inferred from direct assay PubMed 10844024. Source: RGD

protein homodimerization activity

Inferred from direct assay PubMed 14976213. Source: RGD

receptor binding

Inferred from physical interaction PubMed 14976213. Source: RGD

tubulin binding

Traceable author statement Ref.1. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Gabra3P202365EBI-5273276,EBI-5273284
GlrbP481684EBI-349317,EBI-7069198From a different organism.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 6 (identifier: Q03555-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1 (identifier: Q03555-2)

Also known as: GE124'56;

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MATEGMILTNHDHQIRVGVLTV → MSFPLSPAFTLLHILV
Isoform 2 (identifier: Q03555-3)

Also known as: GE236;

The sequence of this isoform differs from the canonical sequence as follows:
     99-111: Missing.
     256-256: K → KNHPFYTSPAVFMANHGQPIPGLISYSHHATGSADKR
     302-320: Missing.
Isoform 3 (identifier: Q03555-4)

Also known as: GE24'6;

The sequence of this isoform differs from the canonical sequence as follows:
     99-111: Missing.
Isoform 4 (identifier: Q03555-5)

Also known as: GE245;

The sequence of this isoform differs from the canonical sequence as follows:
     302-315: QIRRPDESKGVASR → ARLPSCSSTYSVSE
     316-320: Missing.
Isoform 5 (identifier: Q03555-6)

Also known as: GE26;

The sequence of this isoform differs from the canonical sequence as follows:
     99-111: Missing.
     302-320: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 768768Gephyrin
PRO_0000170965

Regions

Region14 – 166153MPT Mo-transferase
Region153 – 348196Interaction with GABARAP
Region326 – 768443MPT adenylyltransferase
Compositional bias213 – 2186Glu-rich (acidic)

Amino acid modifications

Modified residue2011Phosphoserine By similarity
Modified residue2071Phosphoserine By similarity
Modified residue2791Phosphothreonine By similarity
Modified residue3371Phosphoserine By similarity

Natural variations

Alternative sequence1 – 2222MATEG…GVLTV → MSFPLSPAFTLLHILV in isoform 1.
VSP_003238
Alternative sequence99 – 11113Missing in isoform 5, isoform 2 and isoform 3.
VSP_003239
Alternative sequence2561K → KNHPFYTSPAVFMANHGQPI PGLISYSHHATGSADKR in isoform 2.
VSP_003240
Alternative sequence302 – 32019Missing in isoform 5 and isoform 2.
VSP_003243
Alternative sequence302 – 31514QIRRP…GVASR → ARLPSCSSTYSVSE in isoform 4.
VSP_003241
Alternative sequence316 – 3205Missing in isoform 4.
VSP_003242

Experimental info

Mutagenesis3621F → A: Reduced GLRB binding. Ref.9
Mutagenesis745 – 7462PP → AA: Reduced GLRB binding. Ref.9
Mutagenesis7451P → A: Loss of GLRB binding. Ref.9
Sequence conflict2551A → R Ref.3

Secondary structure

.............................................................................................................. 768
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 6 [UniParc].

Last modified May 16, 2006. Version 3.
Checksum: FAD1B6DD76ED79EA

FASTA76883,266
        10         20         30         40         50         60 
MATEGMILTN HDHQIRVGVL TVSDSCFRNL AEDRSGINLK DLVQDPSLLG GTISAYKIVP 

        70         80         90        100        110        120 
DEIEEIKETL IDWCDEKELN LILTTGGTGF APRDVTPEKF PTFPFCGLQK GATKEVIERE 

       130        140        150        160        170        180 
APGMALAMLM GSLNVTPLGM LSRPVCGIRG KTLIINLPGS KKGSQECFQF ILPALPHAID 

       190        200        210        220        230        240 
LLRDAIVKVK EVHDELEDLP SPPPPLSPPP TTSPHKQTED KGVQCEEEEE EKKDSGVAST 

       250        260        270        280        290        300 
EDSSSSHITA AALAAKIPDS IISRGVQVLP RDTASLSTTP SESPRAQATS RLSTASCPTP 

       310        320        330        340        350        360 
KQIRRPDESK GVASRVGSLK VQSRCSSKEN ILRASHSAVD ITKVARRHRM SPFPLTSMDK 

       370        380        390        400        410        420 
AFITVLEMTP VLGTEIINYR DGMGRVLAQD VYAKDNLPPF PASVKDGYAV RAADGPGDRF 

       430        440        450        460        470        480 
IIGESQAGEQ PTQTVMPGQV MRVTTGAPIP CGADAVVQVE DTELIRESDD GTEELEVRIL 

       490        500        510        520        530        540 
VQARPGQDIR PIGHDIKRGE CVLAKGTHMG PSEIGLLATV GVTEVEVNKF PVVAVMSTGN 

       550        560        570        580        590        600 
ELLNPEDDLL PGKIRDSNRS TLLATIQEHG YPTINLGIVG DNPDDLLNAL NEGISRADVI 

       610        620        630        640        650        660 
ITSGGVSMGE KDYLKQVLDI DLHAQIHFGR VFMKPGLPTT FATLDIDGVR KIIFALPGNP 

       670        680        690        700        710        720 
VSAVVTCNLF VVPALRKMQG ILDPRPTIIK ARLSCDVKLD PRPEYHRCIL TWHHQEPLPW 

       730        740        750        760 
AQSTGNQMSS RLMSMRSANG LLMLPPKTEQ YVELHKGEVV DVMVIGRL 

« Hide

Isoform 1 (GE124'56) [UniParc].

Checksum: CF467AB5D3BE99BE
Show »

FASTA76282,616
Isoform 2 (GE236) [UniParc].

Checksum: D25D2294184BE3D4
Show »

FASTA77283,638
Isoform 3 (GE24'6) [UniParc].

Checksum: 219EC28CC2910AC1
Show »

FASTA75581,814
Isoform 4 (GE245) [UniParc].

Checksum: 5E6039E40BDA68ED
Show »

FASTA76382,669
Isoform 5 (GE26) [UniParc].

Checksum: B3817E1BE1D4D41B
Show »

FASTA73679,748

References

[1]"Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein."
Prior P., Schmitt B., Grenningloh G., Pribilla I., Multhaup G., Beyreuther K., Maulet Y., Werner P., Langosch D., Kirsch J., Betz H.
Neuron 8:1161-1170(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PARTIAL PROTEIN SEQUENCE.
Strain: Wistar.
Tissue: Brain.
[2]Schmitt B.
Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 255.
[3]"Functional heterogeneity of gephyrins."
Meier J., De Chaldee M., Triller A., Vannier C.
Mol. Cell. Neurosci. 16:566-577(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
[4]"Structural basis of dynamic glycine receptor clustering by gephyrin."
Sola M., Bavro V.N., Timmins J., Franz T., Ricard-Blum S., Schoehn G., Ruigrok R.W.H., Paarmann I., Saiyed T., O'Sullivan G.A., Schmitt B., Betz H., Weissenhorn W.
EMBO J. 23:2510-2519(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 348-768 IN COMPLEX WITH GLRB, SUBUNIT.
[5]"Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons."
Kirsch J., Wolters I., Triller A., Betz H.
Nature 366:745-748(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse."
Kneussel M., Haverkamp S., Fuhrmann J.C., Wang H., Waessle H., Olsen R.W., Betz H.
Proc. Natl. Acad. Sci. U.S.A. 97:8594-8599(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GABARAP.
[7]"The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells."
Stallmeyer B., Schwarz G., Schulze J., Nerlich A., Reiss J., Kirsch J., Mendel R.R.
Proc. Natl. Acad. Sci. U.S.A. 96:1333-1338(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"X-ray crystal structure of the trimeric N-terminal domain of gephyrin."
Sola M., Kneussel M., Heck I.S., Betz H., Weissenhorn W.
J. Biol. Chem. 276:25294-25301(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-201, SUBUNIT.
[9]"Deciphering the structural framework of glycine receptor anchoring by gephyrin."
Kim E.Y., Schrader N., Smolinsky B., Bedet C., Vannier C., Schwarz G., Schindelin H.
EMBO J. 25:1385-1395(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 350-768 IN COMPLEX WITH GLRB, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-362; PRO-745 AND 745-PRO-PRO-746.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66366 mRNA. Translation: CAA47009.2.
PIRJH0681.
RefSeqNP_074056.2. NM_022865.3. [Q03555-6]
UniGeneRn.11032.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IHCX-ray1.90A1-201[»]
1T3EX-ray3.25A/B348-768[»]
2FTSX-ray2.41A350-768[»]
2FU3X-ray2.70A/B350-768[»]
ProteinModelPortalQ03555.
SMRQ03555. Positions 13-194, 350-768.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249211. 8 interactions.
DIPDIP-33263N.
IntActQ03555. 5 interactions.
MINTMINT-241818.

PTM databases

PhosphoSiteQ03555.

Proteomic databases

PaxDbQ03555.
PRIDEQ03555.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID64845.
KEGGrno:64845.
UCSCRGD:69194. rat. [Q03555-1]

Organism-specific databases

CTD10243.
RGD69194. Gphn.

Phylogenomic databases

eggNOGCOG0303.
HOGENOMHOG000280651.
HOVERGENHBG005828.
InParanoidQ03555.
KOK15376.
PhylomeDBQ03555.

Enzyme and pathway databases

UniPathwayUPA00344.

Gene expression databases

GenevestigatorQ03555.

Family and domain databases

Gene3D2.40.340.10. 1 hit.
3.40.980.10. 2 hits.
InterProIPR020817. Mo_cofactor_synthesis.
IPR008284. MoCF_biosynth_CS.
IPR005111. MoeA_C_domain_IV.
IPR005110. MoeA_linker/N.
IPR001453. Mopterin-bd_dom.
[Graphical view]
PfamPF00994. MoCF_biosynth. 2 hits.
PF03454. MoeA_C. 1 hit.
PF03453. MoeA_N. 1 hit.
[Graphical view]
SMARTSM00852. MoCF_biosynth. 2 hits.
[Graphical view]
SUPFAMSSF53218. SSF53218. 2 hits.
SSF63867. SSF63867. 1 hit.
SSF63882. SSF63882. 1 hit.
TIGRFAMsTIGR00177. molyb_syn. 2 hits.
PROSITEPS01078. MOCF_BIOSYNTHESIS_1. 1 hit.
PS01079. MOCF_BIOSYNTHESIS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ03555.
NextBio613764.
PROQ03555.

Entry information

Entry nameGEPH_RAT
AccessionPrimary (citable) accession number: Q03555
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: May 16, 2006
Last modified: June 11, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways