AGA

Protein identityUniProt · HPA

UniProt accession

P20933

Gene

AGA

Ensembl

ENSG00000038002

Chromosome

4

Canonical length

346 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

346 residues, UniProt reviewed canonical sequence.

>P20933|AGA
     1  MARKSNLPVL LVPFLLCQAL VRCSSPLPLV VNTWPFKNAT EAAWRALASG GSALDAVESG
    61  CAMCEREQCD GSVGFGGSPD ELGETTLDAM IMDGTTMDVG AVGDLRRIKN AIGVARKVLE
   121  HTTHTLLVGE SATTFAQSMG FINEDLSTTA SQALHSDWLA RNCQPNYWRN VIPDPSKYCG
   181  PYKPPGILKQ DIPIHKETED DRGHDTIGMV VIHKTGHIAA GTSTNGIKFK IHGRVGDSPI
   241  PGAGAYADDT AGAAAATGNG DILMRFLPSY QAVEYMRRGE DPTIACQKVI SRIQKHFPEF
   301  FGAVICANVT GSYGAACNKL STFTQFSFMV YNSEKNQPTE EKVDCI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AGA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

36 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AGA.

Disease | AllUniProt

Conditions AGA is implicated in, by any mechanism.

• Aspartylglucosaminuria (AGU) MIM:208400

Disease | GeneticClinVar

122 pathogenic / likely-pathogenic of 582 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aspartylglucosaminuria
• Inborn genetic diseases
• Intellectual disability
• ASPARTYLGLUCOSAMINURIA, FINNISH TYPE
• Autism

Disease | AutoantibodyPubMed

Conditions in which antibodies against AGA are reported. Each links to that disease's full target list.

• Celiac Disease 32
• Diabetes Mellitus, Type 1 6
• Schizophrenia 5

ReferencesPubMed · IEDB

Publications for AGA from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.04

gnomAD pLI

0

gnomAD missense Z

-0.45

DepMap mean gene effect

0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• protein deglycosylation
• proteolysis

Molecular functions

• peptidase activity
• N4-(beta-N-acetylglucosaminyl)-L-asparaginase activity

Cellular components

• azurophil granule lumen
• cytoplasm
• endoplasmic reticulum
• extracellular region
• extracellular space
• lysosome

Protein domainsUniProt · Pfam · InterPro

• Peptidase T2, asparaginase 2
• Nucleophile aminohydrolases, N-terminal
• Asparaginase

KeywordsUniProt

• Autocatalytic cleavage
• Disulfide bond
• Glycoprotein
• Hydrolase
• Lysosome
• Protease
• Signal