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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Interacts with SRGAP2 (via SH3 domain) By similarity. Ref.11
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	Molybdenum cofactor deficiency type C (MOCOD type C) [MIM:252150]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1
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 Polymorphism
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 establishment of synaptic specificity at neuromuscular junction Inferred from electronic annotation. Source: Compara molybdopterin cofactor biosynthetic process Traceable author statement. Source: Reactome 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 Ref.10

Modified residue

194

1

Phosphoserine Ref.7 Ref.10

Modified residue

266

1

Phosphothreonine Ref.5

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 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

Secondary structure

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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] [Europe PMC] [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] [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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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.
+	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.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NQX3. 7 interactions.

MINT

MINT-139581.

STRING

9606.ENSP00000303019.

PTM databases

PhosphoSite

Q9NQX3.

Polymorphism databases

DMDM

13431554.

Proteomic databases

PaxDb

Q9NQX3.

PRIDE

Q9NQX3.

Protocols and materials databases

DNASU

10243.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000315266; ENSP00000312771; ENSG00000171723.
ENST00000478722; ENSP00000417901; ENSG00000171723.

GeneID

10243.

KEGG

hsa:10243.

UCSC

uc001xix.3. human.
uc001xiy.3. human.

Organism-specific databases

CTD

10243.

GeneCards

GC14P066974.

HGNC

HGNC:15465. GPHN.

HPA

CAB004419.
HPA003116.
HPA024694.

MIM

252150. phenotype.
603930. gene.

neXtProt

NX_Q9NQX3.

Orphanet

3197. Hereditary hyperekplexia.
308400. Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C.

PharmGKB

PA28840.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0303.

HOGENOM

HOG000280651.

HOVERGEN

HBG005828.

KO

K15376.

OrthoDB

EOG4N30NB.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000171723-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00344.

Gene expression databases

ArrayExpress

Q9NQX3.

Bgee

Q9NQX3.

CleanEx

HS_GPHN.

Genevestigator

Q9NQX3.

GermOnline

ENSG00000171723. Homo sapiens.

Family and domain databases

Gene3D

2.40.340.10. 1 hit.
3.40.980.10. 2 hits.

InterPro

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

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

ChiTaRS

GPHN. human.

EvolutionaryTrace

Q9NQX3.

GenomeRNAi

10243.

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:	May 29, 2013
This is version 124 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.