Q9NQX3 (GEPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Protein existence	Evidence 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 junction › synapse By similarity. Cell junction › synapse › postsynaptic cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasm › cytoskeleton 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.

Ontologies

Keywords
Biological process	Molybdenum cofactor biosynthesis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	ATP-binding Magnesium Metal-binding Molybdenum Nucleotide-binding
Molecular function	Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	Mo-molybdopterin cofactor biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular component	cell 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 function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 736

736

Gephyrin

PRO_0000170964

Regions

Region

14 – 166

153

MPT Mo-transferase

Region

140 – 316

177

Interaction with GABARAP By similarity

Region

326 – 736

411

MPT adenylyltransferase

Amino acid modifications

Modified residue

188

1

Phosphoserine Ref.7

Modified residue

194

1

Phosphoserine Ref.7

Modified residue

266

1

Phosphothreonine Ref.5

Modified residue

270

1

Phosphoserine Ref.6

Modified residue

286

1

Phosphothreonine Ref.5 Ref.6

Modified residue

305

1

Phosphoserine By similarity

Natural variations

Alternative sequence

243

1

K → KKHPFYTSPAVVMAHGEQPI PGLINYSHHSTDER in isoform 2.

VSP_021769

Natural variant

10

1

N → Y in STHE; sporadic case. Ref.10

VAR_044162

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

736

Helix Strand Turn

Details...

Beta strand

16 – 22

7

Helix

24 – 27

4

Helix

34 – 44

11

Turn

46 – 49

4

Beta strand

52 – 59

8

Helix

63 – 75

13

Beta strand

80 – 86

7

Beta strand

89 – 91

3

Helix

96 – 103

8

Beta strand

105 – 107

3

Helix

109 – 122

14

Helix

124 – 128

5

Beta strand

133 – 136

4

Beta strand

139 – 144

6

Helix

148 – 158

11

Helix

159 – 161

3

Helix

162 – 169

8

Helix

175 – 178

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: E2BDA3AD3AB962C0	FASTA	736	79,748
	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
	Isoform 2 [UniParc]. Checksum: 552D5B7BD9AD7452	FASTA	769	83,448
	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 AAKKHPFYTS PAVVMAHGEQ PIPGLINYSH HSTDERIPDS IISRGVQVLP RDTASLSTTP 310 320 330 340 350 360 SESPRAQATS RLSTASCPTP KVQSRCSSKE NILRASHSAV DITKVARRHR MSPFPLTSMD 370 380 390 400 410 420 KAFITVLEMT PVLGTEIINY RDGMGRVLAQ DVYAKDNLPP FPASVKDGYA VRAADGPGDR 430 440 450 460 470 480 FIIGESQAGE QPTQTVMPGQ VMRVTTGAPI PCGADAVVQV EDTELIRESD DGTEELEVRI 490 500 510 520 530 540 LVQARPGQDI RPIGHDIKRG ECVLAKGTHM GPSEIGLLAT VGVTEVEVNK FPVVAVMSTG 550 560 570 580 590 600 NELLNPEDDL LPGKIRDSNR STLLATIQEH GYPTINLGIV GDNPDDLLNA LNEGISRADV 610 620 630 640 650 660 IITSGGVSMG EKDYLKQVLD IDLHAQIHFG RVFMKPGLPT TFATLDIDGV RKIIFALPGN 670 680 690 700 710 720 PVSAVVTCNL FVVPALRKMQ GILDPRPTII KARLSCDVKL DPRPEYHRCI LTWHHQEPLP 730 740 750 760 WAQSTGNQMS SRLMSMRSAN GLLMLPPKTE QYVELHKGEV VDVMVIGRL

References

	« Hide 'large scale' referencesShow '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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

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.

IPI

IPI00016006.
IPI00184477.

RefSeq

NP_001019389.1. NM_001024218.1.
NP_065857.1. NM_020806.4.

UniGene

Hs.208765.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JLJ	X-ray	1.60	A/B/C	1-181	[»]

ProteinModelPortal

Q9NQX3.

SMR

Q9NQX3. Positions 13-181, 318-736.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NQX3. 8 interactions.

STRING

Q9NQX3.

PTM databases

PhosphoSite

Q9NQX3.

Polymorphism databases

DMDM

13431554.

Proteomic databases

PRIDE

Q9NQX3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000315266; ENSP00000312771; ENSG00000171723.

GeneID

10243.

KEGG

hsa:10243.

UCSC

uc001xix.1. human.
uc001xiy.1. human.

Organism-specific databases

CTD

10243.

GeneCards

GC14P066974.

HGNC

HGNC:15465. GPHN.

HPA

CAB004419.
HPA003116.
HPA024694.

MIM

149400. phenotype.
252150. phenotype.
603930. gene.

neXtProt

NX_Q9NQX3.

Orphanet

833. Encephalopathy due to sulfite oxidase deficiency.
3197. Hereditary hyperekplexia.

PharmGKB

PA28840.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000016577.

HOVERGEN

HBG005828.

OMA

RDVTPEX.

OrthoDB

EOG4N30NB.

PhylomeDB

Q9NQX3.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9NQX3.

Bgee

Q9NQX3.

CleanEx

HS_GPHN.

Genevestigator

Q9NQX3.

GermOnline

ENSG00000171723. Homo sapiens.

Family and domain databases

InterPro

IPR020817. Mo_cofactor_synthesis.
IPR008284. MoCF_biosynth_CS.
IPR005111. MoeA_C_domain_IV.
IPR005110. MoeA_linker/N.
IPR001453. Mopterin-bd.
[Graphical view]

Gene3D

G3DSA:2.40.340.10. G3DSA:2.40.340.10. 1 hit.
G3DSA:3.40.980.10. MPT_bd. 2 hits.

KO

K15376.

Pfam

PF00994. MoCF_biosynth. 2 hits.
PF03454. MoeA_C. 1 hit.
PF03453. MoeA_N. 1 hit.
[Graphical view]

SMART

SM00852. MoCF_biosynth. 2 hits.
[Graphical view]

SUPFAM

SSF53218. MoCF_biosynth. 2 hits.
SSF63867. MoeA_C. 1 hit.
SSF63882. MoeA_N. 1 hit.

TIGRFAMs

TIGR00177. Molyb_syn. 2 hits.

PROSITE

PS01078. MOCF_BIOSYNTHESIS_1. 1 hit.
PS01079. MOCF_BIOSYNTHESIS_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

38806.

SOURCE

Search...

Entry information

Entry name

GEPH_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.