GMPS guanine monphosphate synthetase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GMPSprovided by HGNC
Official Full Name: guanine monphosphate synthetaseprovided by HGNC
Primary source: HGNC:4378
See related: Ensembl:ENSG00000163655; HPRD:10927; MIM:600358; Vega:OTTHUMG00000158551
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 3q24

Sequence :: Chromosome: 3; NC_000003.11 (155588325..155655521)

See GMPS in Epigenomics, MapViewer

Chromosome 3 - NC_000003.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

analysis of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase
Title: Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase.
Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
Title: Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data.
Observational study of genotype prevalence. (HuGE Navigator)
Title: Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese individuals.

Submit: New GeneRIF Correction

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Familial acute myeloid leukemia (AML) with mutated CEBPA is defined as AML in which a germline CEBPA mutation is present in a family in which multiple individuals have AML. In contrast, sporadic AML with mutated CEBPA is defined as AML in which a CEBPA mutation is identified in somatic (i.e., leukemic) cells but not in germline (i.e., non-leukemic) cells. Too few persons with familial AML with mutated CEBPA have been reported to be certain about the natural history of the disease. The age of onset of familial AML with mutated CEBPA appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age four years and older than age 50 years. The prognosis of individuals with familial AML with mutated CEBPA appears to be favorable (~50%-65% overall survival) compared to the ~25%-40% overall survival of those who have normal karyotype AML but no germline CEPBA mutation. Individuals with familial AML with mutated CEBPA who have been cured of their initial disease may be at greater risk of developing additional malignant clones than persons with sporadic disease.

Diagnosis Testing

CEBPA mutations are found in the leukemic cells of approximately 9% of persons with AML, including 15%-18% of persons with normal-karyotype AML; however, few of these individuals have a germline mutation. Detection of a germline CEBPA mutation in a specimen that contains only non-leukemic cells from an individual with AML or detection of a germline CEBPA mutation in a member of a pedigree in which more than one family member has had AML or myelodysplastic syndrome (MDS) establishes the diagnosis of familial AML with mutated CEBPA. Molecular genetic testing of CEBPA is available on a clinical basis.

Genetic Counseling

Familial AML with mutated CEBPA is inherited in an autosomal dominant manner. The proportion of cases caused by a de novo germline mutation is unknown; currently, all seven reported affected individuals have had an affected parent. Each child of an affected individual has a 50% chance of inheriting the germline mutation. No laboratories offering molecular genetic testing for prenatal diagnosis of familial AML with mutated CEBPA are listed in the GeneTests Laboratory Directory; however, prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing germline mutation has been identified. Requests for prenatal testing for conditions that do not affect intellect and have treatment available are not common.

References

PMID: 20963938

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P49915	Q6EEV6	SUMO4	HPRD	PubMed
BioGRID:114360	BioGRID:115806	AGPAT2	BioGRID	PubMed	Two-hybrid
BioGRID:114360	BioGRID:106696	AHCY	BioGRID	PubMed	Co-fractionation
BioGRID:114360	BioGRID:106849	APRT	BioGRID	PubMed	Co-fractionation
BioGRID:114360	BioGRID:118855	BABAM1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:123254	COASY	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:114030	CUL3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:122485	DDA1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:122597	EFHD2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:108340	ENO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:108621	FN1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:109883	ITGA4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:110611	MTAP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:110921	PNP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:119524	PPME1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:119531	PRKAG2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:111684	PSMD5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:111799	RAB1A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:111887	RCN1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:119602	SIRT7	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:132223	SUMO4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:114745	TCEAL1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:113115	TSTA3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:114360	BioGRID:113622	USP7	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-purification
BioGRID:114360	BioGRID:113255	VCAM1	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Drug metabolism - other enzymes, organism-specific biosystem (from KEGG)
Drug metabolism - other enzymes, organism-specific biosystem
Drug metabolism - other enzymes
Drug metabolism - other enzymes, conserved biosystem (from KEGG)
Drug metabolism - other enzymes, conserved biosystem
Drug metabolism - other enzymes
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, organism-specific biosystem (from KEGG)
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Purine metabolism
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, conserved biosystem (from KEGG)
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Purine metabolism
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of nucleotides, organism-specific biosystem (from REACTOME)
Metabolism of nucleotides, organism-specific biosystemNucleotides and their derivatives are used for short-term energy storage (ATP, GTP), for intra- and extra-cellular signaling (cAMP; adenosine), as enzyme cofactors (NAD, FAD), and for the synthesis o...
Purine metabolism, organism-specific biosystem (from KEGG)
Purine metabolism, organism-specific biosystem
Purine metabolism
Purine metabolism, organism-specific biosystem (from REACTOME)
Purine metabolism, organism-specific biosystemThe events of human purine metabolism are conveniently, if somewhat arbitrarily, grouped into four pathways: de novo synthesis of inosine 5'-monophosphate (IMP), the biosynthesis of other purine ribo...
Purine metabolism, conserved biosystem (from KEGG)
Purine metabolism, conserved biosystem
Purine metabolism
Purine ribonucleoside monophosphate biosynthesis, organism-specific biosystem (from REACTOME)
Purine ribonucleoside monophosphate biosynthesis, organism-specific biosystemThe purine ribonucleotide inosine 5'-monophosphate (IMP) is assembled on 5-phospho-alpha-D-ribose 1-diphosphate (PRPP), with atoms derived from aspartate, glutamine, glycine, N10-formyl-tetrahydrofol...
purine nucleotides de novo biosynthesis II, organism-specific biosystem (from BIOCYC)
purine nucleotides de novo biosynthesis II, organism-specific biosystem
purine nucleotides de novo biosynthesis II

General gene information

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Markers

RH121689 (e-PCR)
- UniSTS:134428

D3S4088 (e-PCR)
- UniSTS:34338

RH93796 (e-PCR)
- UniSTS:92995

SHGC-16466 (e-PCR)
- UniSTS:36690

D3S3587 (e-PCR), detects polymorphism
- UniSTS:28536

SHGC-50194 (e-PCR)
- UniSTS:8859

SHGC-84195 (e-PCR)
- UniSTS:104690

Genotypes

Related pseudogene(s)

1 found Review record(s) in Gene

Homology

Homologs of the GMPS gene: The GMPS gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and C.elegans.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
GMP synthase (glutamine-hydrolyzing) activity	IEA Inferred from Electronic Annotation more info
GMP synthase activity	TAS Traceable Author Statement more info	PubMed
pyrophosphatase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
glutamine metabolic process	IEA Inferred from Electronic Annotation more info
nucleobase-containing small molecule metabolic process	TAS Traceable Author Statement more info
purine nucleobase biosynthetic process	TAS Traceable Author Statement more info	PubMed
purine nucleobase metabolic process	TAS Traceable Author Statement more info
purine ribonucleoside monophosphate biosynthetic process	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: GMP synthase [glutamine-hydrolyzing]

Names: GMP synthase [glutamine-hydrolyzing]; GMP synthase; GMP synthetase; MLL/GMPS fusion protein; glutamine amidotransferase; guanosine 5'-monophosphate synthase

NP_003866.1

EC 6.3.5.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_023247.1 RefSeqGene

Range

5001..72197

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003875.2 → NP_003866.1 GMP synthase [glutamine-hydrolyzing]

Status: REVIEWED

Source sequence(s)

BC012178, BG721087, CB159072

Consensus CDS

CCDS46941.1

UniProtKB/TrEMBL

A8K639

UniProtKB/Swiss-Prot

P49915

Related

ENSP00000295920, OTTHUMP00000213049, ENST00000295920, OTTHUMT00000351261

Conserved Domains (4) summary

cd01997
Location:238 – 562
Blast Score: 784

GMP_synthase_C; The C-terminal domain of GMP synthetase. It contains two subdomains; the ATP pyrophosphatase domain which closes to the N-termial and the dimerization domain at C-terminal end. The ATP-PPase is a twisted, five-stranded parallel beta-sheet sandwiched ...

cd01742
Location:28 – 207
Blast Score: 764

GATase1_GMP_Synthase; Type 1 glutamine amidotransferase (GATase1) domain found in GMP synthetase

PRK00074
Location:28 – 562
Blast Score: 1326

guaA; GMP synthase; Reviewed

pfam00958
Location:599 – 692
Blast Score: 212

GMP_synt_C; GMP synthase C terminal domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000003.11 Reference GRCh37.p10 Primary Assembly

Range

155588325..155655521

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000135.1 Alternate HuRef

Range

152982759..153049917

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018914.1 Alternate CHM1_1.0

Range

155569911..155637205

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01058846.1 (45245..74663)	None
genomic	ABBA01058847.1	None
genomic	ABBA01058848.1	None
genomic	AC067721.22 (147978..170949)	None
genomic	AC104472.14	None
genomic	AC140753.4 (2005..27264)	None
genomic	AMYH01013596.1 (88626..104710)	None
genomic	AMYH01013597.1	None
genomic	CH471052.2	EAW78740.1
		EAW78741.1
genomic	HB946314.1	CBG07889.1
genomic	HD003724.1	CBV21411.1
mRNA	AK223399.1	BAD97119.1
mRNA	AK291504.1	BAF84193.1
mRNA	AK300787.1	BAG62449.1
mRNA	AK302148.1	BAG63519.1
mRNA	AK315832.1	BAF98723.1
mRNA	BC012178.1	AAH12178.1
mRNA	BG721087.1	None
mRNA	CB159072.1	None
mRNA	U10860.1	AAA60331.1
other-genetic	DQ896621.2	ABM87620.1
other-genetic	EU176462.1	ABW03913.1