AGA aspartylglucosaminidase [Homo sapiens (human)] - Gene

Summary

Official Symbol: AGAprovided by HGNC
Official Full Name: aspartylglucosaminidaseprovided by HGNC
Primary source: HGNC:HGNC:318
See related: Ensembl:ENSG00000038002 MIM:613228; AllianceGenome:HGNC:318
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
Also known as: GA; AGU; ASRG
Summary: This gene encodes a member of the N-terminal nucleophile (Ntn) hydrolase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta chains that comprise the mature enzyme. This enzyme is involved in the catabolism of N-linked oligosaccharides of glycoproteins. It cleaves asparagine from N-acetylglucosamines as one of the final steps in the lysosomal breakdown of glycoproteins. Mutations in this gene are associated with the lysosomal storage disease aspartylglycosaminuria that results in progressive neurodegeneration. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is subject to proteolytic processing. [provided by RefSeq, Nov 2015]
Expression: Ubiquitous expression in thyroid (RPKM 10.5), testis (RPKM 10.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q34.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (177430774..177442437, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (180769443..180781108, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (178351928..178363591, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

T99K variant of glycosylasparaginase shows a new structural mechanism of the genetic disease aspartylglucosaminuria
Title: The T99K variant of glycosylasparaginase shows a new structural mechanism of the genetic disease aspartylglucosaminuria.
Determination a 1.6 A-resolution structure of the Finnish AGU model and building of an enzyme-substrate complex to provide a structural basis for analyzing the negative effects of the point mutation on KM and kcat of the mature enzyme.
Title: Biochemical and structural insights into an allelic variant causing the lysosomal storage disorder - aspartylglucosaminuria.
1.8A resolution crystal structure of mature G172D mutant of a model missense GA corresponding to a Canadian aspartylglucosaminuria allele; studied the effect of its single amino acid change on substrate processing
Title: Crystal structure of a mutant glycosylasparaginase shedding light on aspartylglycosaminuria-causing mechanism as well as on hydrolysis of non-chitobiose substrate.
We show that gene-silenced cells show specifically reduced AGA activity and store globotriaosylceramide. In gene-silenced cells, release of the neurotransmitter acetylcholine is significantly reduced, demonstrating that this model may be used to study specific neuronal functions such as neurotransmitter release in Fabry disease
Title: Development of a model system for neuronal dysfunction in Fabry disease.
study reports 2 novel aspartylglucosaminidase gene mutations, one in Qatari twins with an early, perinatal presentation not previously described for aspartylglucosaminuria and the other in 3 Turkish children with newly diagnosed aspartylglucosaminuria and a more classical disease course
Title: Aspartylglucosaminuria: unusual neonatal presentation in Qatari twins with a novel aspartylglucosaminidase gene mutation and 3 new cases in a Turkish family.
[review] Natural killer (NK) cell tumors, subtypes of myeloid leukemias and T-cell lymphomas respond to ASNase; ovarian carcinomas and other solid tumors have been proposed as additional targets for ASNase, with a potential role for glutaminase. activity.
Title: Expanding targets for a metabolic therapy of cancer: L-asparaginase.
Increased AGA plasma activity, although a consistent finding in congenital disorders of glycosylation patients, is not specific to this group of disorders.
Title: Plasma lysosomal enzyme activities in congenital disorders of glycosylation, galactosemia and fructosemia.
The amino acid substitutions in aspartylglucosaminidase responsible for aspartylglucosaminuria were classified and divided in three groups.
Title: Structural basis of aspartylglucosaminuria.
Molecular mechanism for the autoproteolytic activation of aspartylglucosaminidase.
Title: Autoproteolytic activation of human aspartylglucosaminidase.
A new point mutation, c.44T>G, found in a Finnish compound heterozygote causes a L15R AA substitution in the signal sequence of the AGA enzyme, affecting AGA translocation by altering a critical hydrophobic core structure in the signal sequence.
Title: A novel aspartylglucosaminuria mutation affects translocation of aspartylglucosaminidase.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Aspartylglucosaminuria MedGen: C0268225 OMIM: 208400 GeneReviews: Aspartylglucosaminuria	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study for biomarker identification of Rapamycin and Everolimus using a lymphoblastoid cell line system. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of serum selenium concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:607621 (e-PCR)
- UniSTS:158242

STS-X55330 (e-PCR)
- UniSTS:28451

GDB:607635 (e-PCR)
- UniSTS:158246

GDB:607636 (e-PCR)
- UniSTS:158247

GDB:607637 (e-PCR)
- UniSTS:158248

GDB:607638 (e-PCR)
- UniSTS:158249

GDB:607643 (e-PCR)
- UniSTS:158251

GDB:607646 (e-PCR)
- UniSTS:158252

GDB:607647 (e-PCR)
- UniSTS:158253

GDB:607648 (e-PCR)
- UniSTS:158254

D4S3226 (e-PCR)
- UniSTS:80194

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity	IBA Inferred from Biological aspect of Ancestor more info
enables N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity	IDA Inferred from Direct Assay more info	PubMed
enables N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables peptidase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in protein deglycosylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein deglycosylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in azurophil granule lumen	TAS Traceable Author Statement more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in lysosome	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase

Names: N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase; aspartylglucosylamine deaspartylase; glycosylasparaginase

NP_000018.2

EC 3.5.1.26

NP_001165459.1

EC 3.5.1.26

XP_047305678.1

EC 3.5.1.26

XP_054205122.1

EC 3.5.1.26

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_011845.2 RefSeqGene

Range

5067..16730

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000027.4 → NP_000018.2 N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase isoform 1 preproprotein

See identical proteins and their annotated locations for NP_000018.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC027627, AW467768, BC012392, BM968469, DA346002

Consensus CDS

CCDS3829.1

UniProtKB/Swiss-Prot

B2R7H2, D3DP47, P20933, Q4W5Q2, Q6FHN6, Q9UCK6, Q9UCK7, Q9UCK8

Related

ENSP00000264595.2, ENST00000264595.7

Conserved Domains (1) summary

cd04513
Location:29 → 332

Glycosylasparaginase; Glycosylasparaginase and similar proteins
NM_001171988.2 → NP_001165459.1 N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses two alternate in-frame splice sites in the central coding region compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AC027627, AW467768, BC012392, BM968469, DA346002

UniProtKB/Swiss-Prot

P20933

Conserved Domains (1) summary

cd04513
Location:29 → 322

Glycosylasparaginase; Glycosylasparaginase and similar proteins

RNA

NR_033655.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AA490958, AC027627, AC078881, CX869892, DA346002