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Q9NQX3 (GEPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 109. 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)
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. Ref.9

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

Defects in GPHN are the cause of molybdenum cofactor deficiency type C (MOCOD type C) [MIM:252150]. MOCOD type C is an autosomal recessive disease which leads to the pleiotropic loss of all molybdoenzyme activities and is characterized by severe neurological damage, neonatal seizures and early childhood death. Ref.1

Defects in GPHN are a cause of startle disease (STHE) [MIM:149400]; also known as hyperekplexia. STHE is a genetically heterogeneous neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli. Ref.1 Ref.10

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.

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
Modified residue1941Phosphoserine Ref.7
Modified residue2661Phosphothreonine Ref.5
Modified residue2701Phosphoserine Ref.6
Modified residue2861Phosphothreonine Ref.5 Ref.6
Modified residue3051Phosphoserine By similarity

Natural variations

Alternative sequence2431K → KKHPFYTSPAVVMAHGEQPI PGLINYSHHSTDER in isoform 2.
VSP_021769
Natural variant101N → Y in STHE; sporadic case. Ref.10
VAR_044162

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: 11095995] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DISEASE.
[2]"The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells."
David-Watine B.
Gene 271:239-245(2001) [PubMed: 11418245] [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: 10718198] [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: 15489334] [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: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-266 AND THR-286, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[6]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-270 AND THR-286, MASS SPECTROMETRY.
Tissue: Embryonic kidney.
[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: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188 AND SER-194, MASS SPECTROMETRY.
Tissue: Leukemic T-cell.
[8]"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: 21269460] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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: 11554796] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-181, SUBUNIT.
[10]"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: 12684523] [Abstract]
Cited for: VARIANT STHE TYR-10.
+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.
IPIIPI00016006.
IPI00184477.
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...

Protein-protein interaction databases

IntActQ9NQX3. 8 interactions.
STRINGQ9NQX3.

PTM databases

PhosphoSiteQ9NQX3.

Polymorphism databases

DMDM13431554.

Proteomic databases

PRIDEQ9NQX3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315266; ENSP00000312771; ENSG00000171723.
GeneID10243.
KEGGhsa:10243.
UCSCuc001xix.1. human.
uc001xiy.1. human.

Organism-specific databases

CTD10243.
GeneCardsGC14P066974.
HGNCHGNC:15465. GPHN.
HPACAB004419.
HPA003116.
HPA024694.
MIM149400. phenotype.
252150. phenotype.
603930. gene.
neXtProtNX_Q9NQX3.
Orphanet833. Encephalopathy due to sulfite oxidase deficiency.
3197. Hereditary hyperekplexia.
PharmGKBPA28840.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

GeneTreeENSGT00390000016577.
HOVERGENHBG005828.
OMARDVTPEX.
OrthoDBEOG4N30NB.
PhylomeDBQ9NQX3.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9NQX3.
BgeeQ9NQX3.
CleanExHS_GPHN.
GenevestigatorQ9NQX3.
GermOnlineENSG00000171723. Homo sapiens.

Family and domain databases

InterProIPR020817. Mo_cofactor_synthesis.
IPR008284. MoCF_biosynth_CS.
IPR005111. MoeA_C_domain_IV.
IPR005110. MoeA_linker/N.
IPR001453. Mopterin-bd.
[Graphical view]
Gene3DG3DSA:2.40.340.10. G3DSA:2.40.340.10. 1 hit.
G3DSA:3.40.980.10. MPT_bd. 2 hits.
KOK15376.
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. MoCF_biosynth. 2 hits.
SSF63867. MoeA_C. 1 hit.
SSF63882. MoeA_N. 1 hit.
TIGRFAMsTIGR00177. Molyb_syn. 2 hits.
PROSITEPS01078. MOCF_BIOSYNTHESIS_1. 1 hit.
PS01079. MOCF_BIOSYNTHESIS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio38806.
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: January 25, 2012
This is version 109 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

Human chromosome 14

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families