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Q9NQX3 (GEPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gephyrin

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, KIAA1385
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length736 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.

Catalytic activity

ATP + molybdopterin = diphosphate + adenylyl-molybdopterin.

Adenylyl-molybdopterin + molybdate = molybdenum cofactor + AMP.

Cofactor

Magnesium By similarity.

Enzyme regulation

Inhibited by copper and tungsten By similarity.

Pathway

Cofactor biosynthesis; molybdopterin biosynthesis.

Subunit structure

Homotrimer. Interacts with GABARAP By similarity. Interacts with SRGAP2 (via SH3 domain) By similarity. Ref.11

Subcellular location

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

Involvement in disease

Molybdenum cofactor deficiency, complementation group C (MOCODC) [MIM:615501]: A form of molybdenum cofactor deficiency, an autosomal recessive metabolic disorder leading to the pleiotropic loss of molybdoenzyme activities. It is clinically characterized by onset in infancy of poor feeding, intractable seizures, severe psychomotor retardation, and death in early childhood in most patients.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.13

Sequence similarities

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

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

Sequence caution

The sequence BAA92623.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

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

Inferred from electronic annotation. Source: UniProtKB-KW

establishment of synaptic specificity at neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

molybdopterin cofactor biosynthetic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   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 electronic annotation. Source: UniProtKB-EC

molybdopterin molybdotransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

transferase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NQX3-1)

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 2 (identifier: Q9NQX3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     243-243: K → KKHPFYTSPAVVMAHGEQPIPGLINYSHHSTDER

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736Gephyrin
PRO_0000170964

Regions

Region14 – 166153MPT Mo-transferase
Region140 – 316177Interaction with GABARAP By similarity
Region326 – 736411MPT adenylyltransferase

Amino acid modifications

Modified residue1881Phosphoserine Ref.7 Ref.10
Modified residue1941Phosphoserine Ref.7 Ref.10
Modified residue2661Phosphothreonine Ref.5
Modified residue3051Phosphoserine By similarity

Natural variations

Alternative sequence2431K → KKHPFYTSPAVVMAHGEQPI PGLINYSHHSTDER in isoform 2.
VSP_021769
Natural variant101N → Y Found in a patient with hyperekplexia; unknown pathological significance; does not affect the structural lattices formed by gephyrin. Ref.12
Corresponds to variant rs121908539 [ dbSNP | Ensembl ].
VAR_044162
Natural variant5801D → A in MOCODC. Ref.13
VAR_070275

Secondary structure

................................... 736
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: E2BDA3AD3AB962C0

FASTA73679,748
        10         20         30         40         50         60 
MATEGMILTN HDHQIRVGVL TVSDSCFRNL AEDRSGINLK DLVQDPSLLG GTISAYKIVP 

        70         80         90        100        110        120 
DEIEEIKETL IDWCDEKELN LILTTGGTGF APRDVTPEAT KEVIEREAPG MALAMLMGSL 

       130        140        150        160        170        180 
NVTPLGMLSR PVCGIRGKTL IINLPGSKKG SQECFQFILP ALPHAIDLLR DAIVKVKEVH 

       190        200        210        220        230        240 
DELEDLPSPP PPLSPPPTTS PHKQTEDKGV QCEEEEEEKK DSGVASTEDS SSSHITAAAI 

       250        260        270        280        290        300 
AAKIPDSIIS RGVQVLPRDT ASLSTTPSES PRAQATSRLS TASCPTPKVQ SRCSSKENIL 

       310        320        330        340        350        360 
RASHSAVDIT KVARRHRMSP FPLTSMDKAF ITVLEMTPVL GTEIINYRDG MGRVLAQDVY 

       370        380        390        400        410        420 
AKDNLPPFPA SVKDGYAVRA ADGPGDRFII GESQAGEQPT QTVMPGQVMR VTTGAPIPCG 

       430        440        450        460        470        480 
ADAVVQVEDT ELIRESDDGT EELEVRILVQ ARPGQDIRPI GHDIKRGECV LAKGTHMGPS 

       490        500        510        520        530        540 
EIGLLATVGV TEVEVNKFPV VAVMSTGNEL LNPEDDLLPG KIRDSNRSTL LATIQEHGYP 

       550        560        570        580        590        600 
TINLGIVGDN PDDLLNALNE GISRADVIIT SGGVSMGEKD YLKQVLDIDL HAQIHFGRVF 

       610        620        630        640        650        660 
MKPGLPTTFA TLDIDGVRKI IFALPGNPVS AVVTCNLFVV PALRKMQGIL DPRPTIIKAR 

       670        680        690        700        710        720 
LSCDVKLDPR PEYHRCILTW HHQEPLPWAQ STGNQMSSRL MSMRSANGLL MLPPKTEQYV 

       730 
ELHKGEVVDV MVIGRL 

« Hide

Isoform 2 [UniParc].

Checksum: 552D5B7BD9AD7452
Show »

FASTA76983,448

References

« Hide 'large scale' references
[1]"A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency."
Reiss J., Gross-Hardt S., Christensen E., Schmidt P., Mendel R.R., Schwarz G.
Am. J. Hum. Genet. 68:208-213(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN MOCODC.
[2]"The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells."
David-Watine B.
Gene 271:239-245(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Kidney.
[3]"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."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[5]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-266, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-194, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-194, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications."
Schwarz G., Schrader N., Mendel R.R., Hecht H.-J., Schindelin H.
J. Mol. Biol. 312:405-418(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-181, SUBUNIT.
[12]"Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia."
Rees M.I., Harvey K., Ward H., White J.H., Evans L., Duguid I.C., Hsu C.-C., Coleman S.L., Miller J., Baer K., Waldvogel H.J., Gibbon F., Smart T.G., Owen M.J., Harvey R.J., Snell R.G.
J. Biol. Chem. 278:24688-24696(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-10, CHARACTERIZATION OF VARIANT TYR-10.
[13]"A GPHN point mutation leading to molybdenum cofactor deficiency."
Reiss J., Lenz U., Aquaviva-Bourdain C., Joriot-Chekaf S., Mention-Mulliez K., Holder-Espinasse M.
Clin. Genet. 80:598-599(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MOCODC ALA-580.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF272663 mRNA. Translation: AAF81785.1.
AJ272343 mRNA. Translation: CAC10537.1.
AB037806 mRNA. Translation: BAA92623.1. Different initiation.
BC030016 mRNA. Translation: AAH30016.1.
RefSeqNP_001019389.1. NM_001024218.1.
NP_065857.1. NM_020806.4.
UniGeneHs.208765.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JLJX-ray1.60A/B/C1-181[»]
ProteinModelPortalQ9NQX3.
SMRQ9NQX3. Positions 13-181, 318-736.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115537. 20 interactions.
IntActQ9NQX3. 8 interactions.
MINTMINT-139581.
STRING9606.ENSP00000303019.

PTM databases

PhosphoSiteQ9NQX3.

Polymorphism databases

DMDM13431554.

Proteomic databases

PaxDbQ9NQX3.
PRIDEQ9NQX3.

Protocols and materials databases

DNASU10243.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315266; ENSP00000312771; ENSG00000171723. [Q9NQX3-1]
ENST00000478722; ENSP00000417901; ENSG00000171723. [Q9NQX3-2]
GeneID10243.
KEGGhsa:10243.
UCSCuc001xix.3. human. [Q9NQX3-2]
uc001xiy.3. human. [Q9NQX3-1]

Organism-specific databases

CTD10243.
GeneCardsGC14P066974.
HGNCHGNC:15465. GPHN.
HPACAB004419.
HPA003116.
HPA024694.
MIM603930. gene.
615501. phenotype.
neXtProtNX_Q9NQX3.
Orphanet3197. Hereditary hyperekplexia.
308400. Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.
PharmGKBPA28840.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0303.
HOGENOMHOG000280651.
HOVERGENHBG005828.
KOK15376.
OrthoDBEOG70087N.
PhylomeDBQ9NQX3.
TreeFamTF300902.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000171723-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00344.

Gene expression databases

ArrayExpressQ9NQX3.
BgeeQ9NQX3.
CleanExHS_GPHN.
GenevestigatorQ9NQX3.

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

ChiTaRSGPHN. human.
EvolutionaryTraceQ9NQX3.
GeneWikiGPHN.
GenomeRNAi10243.
NextBio38806.
PROQ9NQX3.
SOURCESearch...

Entry information

Entry nameGEPH_HUMAN
AccessionPrimary (citable) accession number: Q9NQX3
Secondary accession number(s): Q9H4E9, Q9P2G2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM