AGA aspartylglucosaminidase[Homo sapiens]
Gene ID: 175, updated on 3-Jul-2016


SUMMARY
-------------------------------------------------------------------------------------------------

Official Symbol: AGA (provided by HGNC)
Official full name: aspartylglucosaminidase (provided by HGNC)
Primary source: HGNC:HGNC:318
See related: Ensembl:ENSG00000038002; HPRD:01949; MIM:613228; Vega:OTTHUMG00000160723
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]

Orthologsall (/gene/?Term=ortholog_gene_175[group]), mouse (http://www.ncbi.nlm.nih.gov/gene/11593)

GENOMIC CONTEXT
-------------------------------------------------------------------------------------------------

See AGA in: 	Epigenomics: http://130.14.22.53/epigenomics/view/genome/175?term=AGA
	MapViewer: /mapview/map_search.cgi?direct=on&amp;idtype=gene&amp;id=175

Location: 4q34.3

Annotation release	Status	Assembly	Chromosome	Location
-------------------------------------------------------------------------------------------------
108	current	GRCh38.p7 (GCF_000001405.33)	4	NC_000004.12 (177430774..177442503, complement) 
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (178351928..178363657, complement) 
Exont count: 9


BIBLIOGRAPHY
-------------------------------------------------------------------------------------------------


Related Articles in PubMed

1. Aspartylglucosaminuria: unusual neonatal presentation in Qatari twins with a
novel aspartylglucosaminidase gene mutation and 3 new cases in a Turkish family. 
Opladen T, . J Child Neurol, 2014 Jan, PMID 23271757.
2. Expanding targets for a metabolic therapy of cancer: L-asparaginase. Covini D, . 
Recent Pat Anticancer Drug Discov, 2012 Jan, PMID 21854356.
3. Plasma lysosomal enzyme activities in congenital disorders of glycosylation,
galactosemia and fructosemia. Michelakakis H, . Clin Chim Acta, 2009 Mar, PMID
19100247.
4. Structural basis of aspartylglucosaminuria. Saito S, . Biochem Biophys Res
Commun, 2008 Dec 26, PMID 18992224.
5. Elevation of plasma aspartylglucosaminidase is a useful marker for the congenital
disorders of glycosylation type I (CDG I). Jackson M, . J Inherit Metab Dis,
2005, PMID 16435229.
6. A novel aspartylglucosaminuria mutation affects translocation of
aspartylglucosaminidase. Saarela J, . Hum Mutat, 2004 Oct, PMID 15365992.

GeneRIFs: Gene References Into Functions

1. 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
2. [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.
3. Increased AGA plasma activity, although a consistent finding in congenital
disorders of glycosylation patients, is not specific to this group of disorders.
4. The amino acid substitutions in aspartylglucosaminidase responsible for
aspartylglucosaminuria were classified and divided in three groups.
5. Molecular mechanism for the autoproteolytic activation of
aspartylglucosaminidase.
6. A new point mutation, c.44T&gt;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.
7. aspartylglucosaminidase may have a role in development of congenital disorders of
glycosylation type I
<pre>
PHENOTYPES
-------------------------------------------------------------------------------------------------

Review eQTL and phenotype association data in this region using PheGenI
	http://www.ncbi.nlm.nih.gov/gap/PheGenI?chr=4&amp;from=177442502&amp;fromto=177442502+177430773&amp;tab=0

Associated conditions
-------------------------------------------------------------------------------------------------
Description	Tests
-------------------------------------------------------------------------------------------------

Aspartylglycosaminuria
	MedGen: C0268225 OMIM:  208400 GeneReviews: <span>Not available</span>	

NHGRI GWAS CatalogGenome-wide association study for biomarker identification of Rapamycin and Everolimus using a lymphoblastoid cell line system.
	NHGRI GWA Catalog		
			
			NHGRI GWA Catalog(http://www.genome.gov/gwastudies/index.cfm?pmid=24009623#result_table)
			PubMed(/pubmed/24009623)Genome-wide association study of serum selenium concentrations.
	NHGRI GWA Catalog		
			
			NHGRI GWA Catalog(http://www.genome.gov/gwastudies/index.cfm?pmid=23698163#result_table)
			PubMed(/pubmed/23698163)No evidence of gene-calcium interactions from genome-wide analysis of colorectal cancer risk.
	NHGRI GWA Catalog		
			
			NHGRI GWA Catalog(http://www.genome.gov/gwastudies/index.cfm?pmid=25192705#result_table)
			PubMed(/pubmed/25192705)</pre>

VARIATION
-------------------------------------------------------------------------------------------------

See variants in ClinVar, http://130.14.22.53/sites/gene/clinvar/?term=AGA[gene]
See studies and variants in dbVar, http://130.14.22.53/sites/gene
See Variation Viewer (GRCh37.p13), http://130.14.22.53/sites/gene/variation/view/?q=175[geneid]&amp;assm=GCF_000001405.25
See Variation Viewer (GRCh38), http://130.14.22.53/sites/gene/variation/view/?q=175[geneid]<pre/><pre>
Genotypes
	See  SNP Geneview Report, http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2FSNP%2Fsnp_ref.cgi%3FlocusId%3D175
	See 1000 Genomes Browser (GCF_000001405.25), http://130.14.22.53/sites/gene/variation/tools/1000genomes/?q=175[geneid]&amp;assm=GCF_000001405.25</pre>


INTERACTION
-------------------------------------------------------------------------------------------------

Description of Gene Interaction table

Product		Interactant	Other Gene    Complex	Source		Pubs
-------------------------------------------------------------------------------------------------

P20933         	P20933         	AGA        		HPRD		PMID: 9737998
P20933         	P02768         	ALB        		HPRD		PMID: 15174051
P20933         	P11717         	IGF2R      		HPRD		PMID: 9362483
Co-purification
BioGRID:106683 	BioGRID:106683 	AGA        		BioGRID		PMID: 9737998
Affinity Capture-MS
BioGRID:106683 	BioGRID:106715 	ALB        		BioGRID		PMID: 15174051
Affinity Capture-MS
BioGRID:106683 	BioGRID:117654 	FBXO6      		BioGRID		PMID: 26186194,22268729
Affinity Capture-MS
BioGRID:106683 	BioGRID:109290 	HBA2       		BioGRID		PMID: 26186194
Affinity Capture-MS
BioGRID:106683 	BioGRID:109293 	HBB        		BioGRID		PMID: 26186194
Affinity Capture-MS
BioGRID:106683 	BioGRID:109721 	IGHG1      		BioGRID		PMID: 26186194
Affinity Capture-MS
BioGRID:106683 	BioGRID:117369 	MOB4       		BioGRID		PMID: 26186194
Affinity Capture-MS
BioGRID:106683 	BioGRID:115709 	ZER1       		BioGRID		PMID: 26186194

Pathways from BioSystems
-------------------------------------------------------------------------------------------------

Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
L-asparagine degradation III (mammalian), conserved biosystem (from BIOCYC)
Lysosome, organism-specific biosystem (from KEGG)
Lysosome, conserved biosystem (from KEGG)
Other glycan degradation, organism-specific biosystem (from KEGG)
Other glycan degradation, conserved biosystem (from KEGG)
asparagine degradation, organism-specific biosystem (from BIOCYC)


GENERAL GENE INFO
-------------------------------------------------------------------------------------------------

Marker
	GDB:607621           	(e-PCR)	Links:UniSTS:158242
	STS-X55330           	(e-PCR)	Links:UniSTS:28451
	GDB:607635           	(e-PCR)	Links:UniSTS:158246
	GDB:607636           	(e-PCR)	Links:UniSTS:158247
	GDB:607637           	(e-PCR)	Links:UniSTS:158248
	GDB:607638           	(e-PCR)	Links:UniSTS:158249
	GDB:607643           	(e-PCR)	Links:UniSTS:158251
	GDB:607646           	(e-PCR)	Links:UniSTS:158252
	GDB:607647           	(e-PCR)	Links:UniSTS:158253
	GDB:607648           	(e-PCR)	Links:UniSTS:158254
	D4S3226              	(e-PCR)	Links:UniSTS:80194

Related pseudogene(s)
	2 foundReview record(s) in Gene, http://130.14.22.53/gene/?Term=related_functional_gene_175%5Bgroup%5D


Homology
	Homologs of the AGA gene
		The AGA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, M.oryzae, A.thaliana, rice, and frog.
	Orthologs from Annotation Pipeline (/gene/?Term=ortholog_gene_175[group]): 
	Map Viewer (Mouse, Rat)


Gene Ontology Provided by GOA (www.ebi.ac.uk/GOA)

Function				      GO ID		Evidence
-------------------------------------------------------------------------------------------------
N4-(beta-N-acetylglucosaminyl)-L-asparag...   GO:0000000	PMID: 1281977
N4-(beta-N-acetylglucosaminyl)-L-asparag...   GO:0000000	PMID: 1904874
peptidase activity                            GO:0000000	-
protein self-association                      GO:0000000	-

Processs				      GO ID		Evidence
-------------------------------------------------------------------------------------------------
protein deglycosylation                       GO:0000000	PMID: 1281977
protein deglycosylation                       GO:0000000	PMID: 1904874
protein maturation                            GO:0000000	-
proteolysis                                   GO:0000000	-

Component				      GO ID		Evidence
-------------------------------------------------------------------------------------------------
endoplasmic reticulum                         GO:0000000	PMID: 8776587
extracellular exosome                         GO:0000000	PMID: 23376485
extracellular space                           GO:0000000	PMID: 25645918
lysosome                                      GO:0000000	PMID: 8776587

GENERAL PROTEIN INFORMATION
-------------------------------------------------------------------------------------------------
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

NCBI REFERENCE SEQUENCES (RefSeq)
-------------------------------------------------------------------------------------------------

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds.
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 section above.

	Genomic
		NG_011845.2 RefSeqGene
		Range   	5000..16729
		Download	GenBank FASTA Sequence Viewer (Graphics) 



	mRNA and Protein(s) 

	NM_000027.3 → NP_000018.2  REVIEWEDN(4)-(beta-N-acetylglucosaminyl)-L-asparaginase isoform 1 preproprotein

	See proteins identical to NP_000018.2 at http://130.14.22.53/protein?LinkName=protein_protein_identical%26from_uid=285002251

	  Description: Transcript Variant: This variant (1) represents...
	  Source sequence(s): AC027627, AW467768, BC012392, BM968469, DA346002 
	  Consensus CDS: CCDS3829.1
	  UniProtKB/Swiss-Prot: P20933

	  Related Ensembl: ENSP00000264595, OTTHUMP00000218812, ENST00000264595, OTTHUMT00000361916
	  Conserved Domains (1)summary
		cd04513: 
		Location:29 - 332
		Glycosylasparaginase; Glycosylasparaginase and similar proteins

	NM_001171988.1 → NP_001165459.1  REVIEWEDN(4)-(beta-N-acetylglucosaminyl)-L-asparaginase isoform 2 precursor
	  Description: Transcript Variant: This variant (2) uses two a...
	  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

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108
The following sections contain reference sequences that belong to a specific genome build. 
This section includes genomic Reference Sequences (RefSeqs) from all assemblies on which 
this gene is annotated, such as RefSeqs for chromosomes and scaffolds (contigs) from both 
reference and alternate assemblies. Model RNAs and proteins are also reported here.

Reference GRCh38.p7 Primary Assembly

	Genomic
		NC_000004.12
		Range   	177430773..177442502, complement
		Download	GenBank FASTA Sequence Viewer (Graphics) 



	RNA

XR_001741155.1 RNA SequenceAlternate CHM1_1.1

	Genomic
		NC_018915.2 Alternate CHM1_1.1
		Range   	178328374..178340108, complement
		Download	GenBank FASTA Sequence Viewer (Graphics) 



RELATED SEQUENCES
-------------------------------------------------------------------------------------------------

Nucleotide			Protein
-------------------------------------------------------------------------------------------------
genomic             		AC027627.6(181307..189665)	None
genomic             		AC078881.5	AAY40915.1
genomic             		AF109147.1	AAD05562.1
genomic             		AMYH02010565.1(13356..25090)	None
genomic             		CH471056.2	EAX04712.1
				EAX04713
				EAX04714
				EAX04715
genomic             		S83096.1	AAD14424.1
genomic             		U91542.1	None
genomic             		X61959.1	CAA43958.1
mRNA                		AA490958.1	None
mRNA                		AK303370.1	BAG64427.1
mRNA                		AK312982.1	BAG35819.1
mRNA                		AW467768.1	None
mRNA                		BC012392.1	AAH12392.1
mRNA                		BM968469.1	None
mRNA                		CR541715.1	CAG46516.1
mRNA                		CX869892.1	None
mRNA                		DA346002.1	None
mRNA                		DA905583.1	None
mRNA                		M60808.1	AAA35901.1
mRNA                		M60809.1	AAA35902.1
mRNA                		M64073.1	AAA35903.1
mRNA                		M64075.1	AAA35904.1
mRNA                		M64076.1	AAA35905.1
mRNA                		M83247.1	AAA36215.1
mRNA                		X55762.1	CAA39288.1
mRNA                		X73071.1	CAA51529.1
other-genetic       		DQ891353.2	ABM82279.1
other-genetic       		DQ894534.2	ABM85460.1

Protein Accession		Links
-------------------------------------------------------------------------------------------------
P20933.2       	GenPept		UniProtKB/Swiss-Prot:P20933.2

GENE LINKOUT
-------------------------------------------------------------------------------------------------
The following LinkOut(www.ncbi.nlm.nih.gov/projects/linkout/index.html) resources
are supplied by external providers. These providers are responsible for
maintaining the links.

Chemical Information
  (Free resource) (free) Interologous Interaction Database
	Interologous Interaction Database
  (Order form) Novus Biologicals
	Primary AntibodiesPrimary AntibodiesLysatesLysatesPeptides and ProteinsPeptides and Proteins

Medical
  (Free resource) (free) Breast Cancer TissueBank Bioinformatics Portal
	Breast Cancer TissueBank Bioinformatics Portal
  (Free resource) (free) Genetics Home Reference
	AGA geneAGA gene
  (Free resource) (free) Pancreatic Expression Database
	Pancreatic Expression Database

Molecular Biology Databases
  (Free resource) (free) BioGPS
	BioGPS
  (Free resource) (free) CREB Target Gene Database
	CREB Target Gene Database
  (Free resource) (free) CutDB, Proteolytic Event Database (part of Proteolysis MAP (PMAP), proteolysis reasoning environment)
	CutDB, Proteolytic Event Database (part of Proteolysis MAP (PMAP), proteolysis reasoning environment)CutDB, Proteolytic Event Database (part of Proteolysis MAP (PMAP), proteolysis reasoning environment)
  (Free resource) (free) Domain Mapping of Disease Mutations
	AGAAGA
  (Free resource) (free) EVEX
	EVEX text mining resourceEVEX text mining resource
  (Order form) GenScript:ORF Clones in your selected vector
	GenScript:ORF Clones in your selected vector
  (Free resource) (free) GeneNetwork
	Records for gene expression in HumanRecords for gene expression in Human
  (Free resource) (free) Genevisible
	AGAAGA
  GoPubMed Proteins
	A selection of literature about the genesA selection of literature about the genes
  (Free resource) (free) HuRef Browser
	HuRef Genome AnnotationHuRef Genome Annotation
  (Free resource) (Free registration required) (free) Human Gene Mutation Database
	Human Gene Mutation Database
  (Free resource) (free) Human eFP Browser
	Human eFP BrowserHuman eFP BrowserHuman eFP Browser
  Ingenuity Pathways Analysis
	Ingenuity Pathways Analysis
  (Free resource) (free) InnateDB
	InnateDB
  (Free resource) (free) InterMine
	InterMine
  (Free resource) (free) Kyoto Encyclopedia of Genes and Genomes
	hsa:175hsa:175
  (Free resource) (free) LSDB from Gene
	Finnish Disease DatabaseFinnish Disease Database
  (Free resource) (free) NextBio
	NextBio
  (Free resource) (free) Nuclear Receptor Signaling Atlas (NURSA)
	Transcriptomine: regulation of the AGA gene by nuclear receptor signaling pathwaysTranscriptomine: regulation of the AGA gene by nuclear receptor signaling pathways
  (Free resource) (free) PhosphoSitePlus
	PhosphoSitePlus® - comprehensive post-translational modification resourcePhosphoSitePlus® - comprehensive post-translational modification resource
  (Free resource) (free) Protein Ontology Consortium
	Protein Ontology Consortium
  (Free resource) (Order form) (free) SeekQuence Research Antibodies
	SeekQuence Research Antibodies
  (Free resource) (free) The Gene Wiki
	The Gene Wiki
  (Free resource) (free) The Weizmann Institute of Science GeneCards and MalaCards databases
	GeneCard for AGAGeneCard for AGA
  (Free resource) (free) iHOP - Information Hyperlinked over Proteins
	iHOP - Information Hyperlinked over Proteins
  (Free resource) (free) iRefWeb - iRefIndex release 9.0 - Consolidated Interactome
	iRefWeb - iRefIndex release 9.0 - Consolidated Interactome
  (Free resource) (free) pfSNP
	pfSNP

Research Materials
  (Order form) Addgene Non-profit plasmid repository
	Get  Plasmids - AddgeneGet  Plasmids - Addgene
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  (Order form) GeneCopoeia Inc.
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  (Order form) Kazusa DNA Research Institute
	Kazusa DNA Research Institute
  LifeSpan BioSciences, Inc.
	LSBio AGA / Aspartylglucosaminidase AntibodiesLSBio AGA / Aspartylglucosaminidase AntibodiesLSBio AGA / Aspartylglucosaminidase ProteinsLSBio AGA / Aspartylglucosaminidase ProteinsLSBio AGA / Aspartylglucosaminidase Blocking PeptidesLSBio AGA / Aspartylglucosaminidase Blocking Peptides
  (Order form) NITE Biological Resource Center
	Human cDNA clones used in NEDO Project / AK303370Human cDNA clones used in NEDO Project / AK303370Human cDNA clones used in NEDO Project / AK312982Human cDNA clones used in NEDO Project / AK312982
  (Order form) PlasmID Repository at Harvard Medical School
	Order full-length cDNA cloneOrder full-length cDNA clone
  (Order form) QIAGEN GeneGlobe
	QIAGEN GeneGlobe
  (Order form) Sino Biological Inc.
	Human AGA Gene cDNA Clone (full-length ORF Clone)Human AGA Gene cDNA Clone (full-length ORF Clone)
  (Order form) antibodies-online
	antibodies-online

Tools
  (Free resource) (free) GeneMANIA
	GeneMANIA