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Protein

Gephyrin

Gene

GPHN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 functionMultifunctional enzyme, Transferase
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

MoonDBiQ9NQX3 Curated
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
MIMi603930 gene
neXtProtiNX_Q9NQX3

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
ProteomicsDBi82221
82222 [Q9NQX3-2]

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
DYNLL1P631673EBI-2371891,EBI-349105

Protein-protein interaction databases

BioGridi115537, 35 interactors
DIPiDIP-41076N
IntActiQ9NQX3, 14 interactors
MINTiQ9NQX3
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

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

CDDicd00887 MoeA, 1 hit
cd00886 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
IPR038987 MoeA-like
IPR005111 MoeA_C_domain_IV
IPR036688 MoeA_C_domain_IV_sf
IPR005110 MoeA_linker/N
IPR036135 MoeA_linker/N_sf
PANTHERiPTHR10192 PTHR10192, 1 hit
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

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:rs121908539EnsemblClinVar.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: July 18, 2018
This is version 172 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, 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

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