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Protein

Gephyrin

Gene

GPHN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules. 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.1 Publication

Catalytic activityi

ATP + molybdopterin = diphosphate + adenylyl-molybdopterin.1 Publication
Adenylyl-molybdopterin + molybdate = molybdenum cofactor + AMP.2 Publications

Cofactori

Mg2+By similarity

Enzyme regulationi

Inhibited by copper and tungsten.By similarity

Pathwayi: molybdopterin biosynthesis

This protein is involved in the pathway molybdopterin biosynthesis, which is part of Cofactor biosynthesis.3 Publications
View all proteins of this organism that are known to be involved in the pathway molybdopterin biosynthesis and in Cofactor biosynthesis.

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • molybdopterin adenylyltransferase activity Source: GO_Central
  • molybdopterin cofactor binding Source: CAFA
  • molybdopterin molybdotransferase activity Source: GO_Central
  • nitrate reductase activity Source: CAFA

GO - Biological processi

  • gamma-aminobutyric acid receptor clustering Source: UniProtKB
  • glycine receptor clustering Source: GO_Central
  • molybdenum incorporation into molybdenum-molybdopterin complex Source: GO_Central
  • molybdopterin cofactor biosynthetic process Source: UniProtKB
  • Mo-molybdopterin cofactor biosynthetic process Source: GO_Central
  • response to metal ion Source: CAFA

Keywordsi

Molecular functionTransferase
Biological processMolybdenum cofactor biosynthesis
LigandATP-binding, Magnesium, Metal-binding, Molybdenum, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000171723-MONOMER.
ReactomeiR-HSA-947581. Molybdenum cofactor biosynthesis.
SIGNORiQ9NQX3.
UniPathwayiUPA00344.

Protein family/group databases

MoonProtiQ9NQX3.

Names & Taxonomyi

Protein namesi
Recommended name:
Gephyrin1 Publication
Including the following 2 domains:
Molybdopterin adenylyltransferase (EC:2.7.7.751 Publication)
Short name:
MPT adenylyltransferase
Alternative name(s):
Domain G
Molybdopterin molybdenumtransferase (EC:2.10.1.12 Publications)
Short name:
MPT Mo-transferase
Alternative name(s):
Domain E
Gene namesi
Name:GPHNImported
Synonyms:GPH, KIAA1385
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000171723.15.
HGNCiHGNC:15465. GPHN.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Molybdenum cofactor deficiency, complementation group C (MOCODC)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615501
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075626375G → D in MOCODC; patient phenotype resembling Dravet syndrome; abolishes postsynaptic clustering of GPHN; decreases cell-surface expression of GABA receptors; impairs postsynaptic currents; catalytically inactive; decreases binding affinity toward GABRA3; decreases binding affinity toward GLRB. 1 Publication1
Natural variantiVAR_070275580D → A in MOCODC; lacks molybdenum cofactor synthesis activity. 2 PublicationsCorresponds to variant dbSNP:rs397518420Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi10243.
GeneReviewsiGPHN.
MalaCardsiGPHN.
MIMi615501. phenotype.
OpenTargetsiENSG00000171723.
Orphaneti3197. Hereditary hyperekplexia.
308400. Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.
PharmGKBiPA28840.

Chemistry databases

DrugBankiDB01942. Formic Acid.
DB03766. Propanoic Acid.

Polymorphism and mutation databases

BioMutaiGPHN.
DMDMi13431554.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001709641 – 736GephyrinAdd BLAST736

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei188PhosphoserineCombined sources1
Modified residuei194PhosphoserineCombined sources1
Modified residuei198PhosphothreonineCombined sources1
Modified residuei200PhosphoserineBy similarity1
Modified residuei262PhosphoserineBy similarity1
Modified residuei265PhosphothreonineBy similarity1
Modified residuei266PhosphothreonineCombined sources1
Modified residuei268PhosphoserineBy similarity1
Modified residuei270PhosphoserineBy similarity1
Modified residuei305PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NQX3.
MaxQBiQ9NQX3.
PaxDbiQ9NQX3.
PeptideAtlasiQ9NQX3.
PRIDEiQ9NQX3.

PTM databases

iPTMnetiQ9NQX3.
PhosphoSitePlusiQ9NQX3.

Expressioni

Gene expression databases

BgeeiENSG00000171723.
CleanExiHS_GPHN.
ExpressionAtlasiQ9NQX3. baseline and differential.
GenevisibleiQ9NQX3. HS.

Organism-specific databases

HPAiCAB004419.
HPA003116.
HPA024694.

Interactioni

Subunit structurei

Homotrimer, homodimer and homooligomer (PubMed:26613940). Interacts with GABARAP (By similarity). Interacts with SRGAP2 (via SH3 domain) (By similarity). Interacts with GABRA3 (PubMed:26613940). Interacts with GLRB (PubMed:26613940, PubMed:12684523). GABRA3 and GLRB occupy overlapping binding sites (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DYNLL1P631672EBI-2371891,EBI-349105

Protein-protein interaction databases

BioGridi115537. 35 interactors.
DIPiDIP-41076N.
IntActiQ9NQX3. 14 interactors.
MINTiMINT-139581.
STRINGi9606.ENSP00000417901.

Structurei

Secondary structure

1736
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 22Combined sources7
Helixi24 – 27Combined sources4
Helixi34 – 44Combined sources11
Turni46 – 49Combined sources4
Beta strandi52 – 59Combined sources8
Helixi63 – 75Combined sources13
Beta strandi80 – 86Combined sources7
Beta strandi89 – 91Combined sources3
Helixi96 – 103Combined sources8
Beta strandi105 – 107Combined sources3
Helixi109 – 122Combined sources14
Helixi124 – 128Combined sources5
Beta strandi133 – 136Combined sources4
Beta strandi139 – 144Combined sources6
Helixi148 – 158Combined sources11
Helixi159 – 161Combined sources3
Helixi162 – 169Combined sources8
Helixi175 – 178Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JLJX-ray1.60A/B/C1-181[»]
ProteinModelPortaliQ9NQX3.
SMRiQ9NQX3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NQX3.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 166MPT Mo-transferaseAdd BLAST153
Regioni140 – 316Interaction with GABARAPBy similarityAdd BLAST177
Regioni326 – 736MPT adenylyltransferaseAdd BLAST411

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2371. Eukaryota.
COG0303. LUCA.
COG0521. LUCA.
GeneTreeiENSGT00390000016577.
HOGENOMiHOG000280651.
HOVERGENiHBG005828.
InParanoidiQ9NQX3.
KOiK15376.
PhylomeDBiQ9NQX3.
TreeFamiTF300902.

Family and domain databases

CDDicd00886. MogA_MoaB. 1 hit.
Gene3Di2.40.340.10. 1 hit.
3.40.980.10. 2 hits.
InterProiView protein in InterPro
IPR036425. MoaB/Mog-like_dom_sf.
IPR001453. MoaB/Mog_dom.
IPR008284. MoCF_biosynth_CS.
IPR005111. MoeA_C_domain_IV.
IPR036688. MoeA_C_domain_IV_sf.
IPR005110. MoeA_linker/N.
IPR036135. MoeA_linker/N_sf.
PfamiView protein in Pfam
PF00994. MoCF_biosynth. 2 hits.
PF03454. MoeA_C. 1 hit.
PF03453. MoeA_N. 1 hit.
SMARTiView protein in SMART
SM00852. MoCF_biosynth. 2 hits.
SUPFAMiSSF53218. SSF53218. 2 hits.
SSF63867. SSF63867. 1 hit.
SSF63882. SSF63882. 1 hit.
TIGRFAMsiTIGR00177. molyb_syn. 2 hits.
PROSITEiView protein in PROSITE
PS01078. MOCF_BIOSYNTHESIS_1. 1 hit.
PS01079. MOCF_BIOSYNTHESIS_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NQX3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MATEGMILTN HDHQIRVGVL TVSDSCFRNL AEDRSGINLK DLVQDPSLLG
60 70 80 90 100
GTISAYKIVP DEIEEIKETL IDWCDEKELN LILTTGGTGF APRDVTPEAT
110 120 130 140 150
KEVIEREAPG MALAMLMGSL NVTPLGMLSR PVCGIRGKTL IINLPGSKKG
160 170 180 190 200
SQECFQFILP ALPHAIDLLR DAIVKVKEVH DELEDLPSPP PPLSPPPTTS
210 220 230 240 250
PHKQTEDKGV QCEEEEEEKK DSGVASTEDS SSSHITAAAI AAKIPDSIIS
260 270 280 290 300
RGVQVLPRDT ASLSTTPSES PRAQATSRLS TASCPTPKVQ SRCSSKENIL
310 320 330 340 350
RASHSAVDIT KVARRHRMSP FPLTSMDKAF ITVLEMTPVL GTEIINYRDG
360 370 380 390 400
MGRVLAQDVY AKDNLPPFPA SVKDGYAVRA ADGPGDRFII GESQAGEQPT
410 420 430 440 450
QTVMPGQVMR VTTGAPIPCG ADAVVQVEDT ELIRESDDGT EELEVRILVQ
460 470 480 490 500
ARPGQDIRPI GHDIKRGECV LAKGTHMGPS EIGLLATVGV TEVEVNKFPV
510 520 530 540 550
VAVMSTGNEL LNPEDDLLPG KIRDSNRSTL LATIQEHGYP TINLGIVGDN
560 570 580 590 600
PDDLLNALNE GISRADVIIT SGGVSMGEKD YLKQVLDIDL HAQIHFGRVF
610 620 630 640 650
MKPGLPTTFA TLDIDGVRKI IFALPGNPVS AVVTCNLFVV PALRKMQGIL
660 670 680 690 700
DPRPTIIKAR LSCDVKLDPR PEYHRCILTW HHQEPLPWAQ STGNQMSSRL
710 720 730
MSMRSANGLL MLPPKTEQYV ELHKGEVVDV MVIGRL
Length:736
Mass (Da):79,748
Last modified:October 1, 2000 - v1
Checksum:iE2BDA3AD3AB962C0
GO
Isoform 2 (identifier: Q9NQX3-2) [UniParc]FASTAAdd to basket

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

Show »
Length:769
Mass (Da):83,448
Checksum:i552D5B7BD9AD7452
GO

Sequence cautioni

Q9NQX3: The sequence BAA92623 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti261A → V in CAC81240 (PubMed:10839351).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04416210N → Y Found in a patient with hyperekplexia; unknown pathological significance; does not disrupt GLRB-GPHN interactions; does not affect the structural lattices formed by GPHN. 1 PublicationCorresponds to variant dbSNP:rs121908539Ensembl.1
Natural variantiVAR_075626375G → D in MOCODC; patient phenotype resembling Dravet syndrome; abolishes postsynaptic clustering of GPHN; decreases cell-surface expression of GABA receptors; impairs postsynaptic currents; catalytically inactive; decreases binding affinity toward GABRA3; decreases binding affinity toward GLRB. 1 Publication1
Natural variantiVAR_070275580D → A in MOCODC; lacks molybdenum cofactor synthesis activity. 2 PublicationsCorresponds to variant dbSNP:rs397518420Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021769243K → KKHPFYTSPAVVMAHGEQPI PGLINYSHHSTDER in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ272033 mRNA. Translation: CAC81240.1.
AF272663 mRNA. Translation: AAF81785.1.
AJ272343 mRNA. Translation: CAC10537.1.
AB037806 mRNA. Translation: BAA92623.1. Different initiation.
BC030016 mRNA. Translation: AAH30016.1.
CCDSiCCDS32103.1. [Q9NQX3-1]
CCDS9777.1. [Q9NQX3-2]
RefSeqiNP_001019389.1. NM_001024218.1. [Q9NQX3-1]
NP_065857.1. NM_020806.4. [Q9NQX3-2]
UniGeneiHs.208765.

Genome annotation databases

EnsembliENST00000315266; ENSP00000312771; ENSG00000171723. [Q9NQX3-1]
ENST00000478722; ENSP00000417901; ENSG00000171723. [Q9NQX3-2]
GeneIDi10243.
KEGGihsa:10243.
UCSCiuc001xix.4. human. [Q9NQX3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGEPH_HUMAN
AccessioniPrimary (citable) accession number: Q9NQX3
Secondary accession number(s): Q96KU4, Q9H4E9, Q9P2G2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 1, 2000
Last modified: October 25, 2017
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families