ADA adenosine deaminase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: ADAprovided by HGNC
Official Full Name: adenosine deaminaseprovided by HGNC
Primary source: HGNC:186
See related: Ensembl:ENSG00000196839; HPRD:00038; MIM:608958; Vega:OTTHUMG00000033081
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: This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine. Various mutations have been described for this gene and have been linked to human diseases. Deficiency in this enzyme causes a form of severe combined immunodeficiency disease (SCID), in which there is dysfunction of both B and T lymphocytes with impaired cellular immunity and decreased production of immunoglobulins, whereas elevated levels of this enzyme have been associated with congenital hemolytic anemia. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 20q13.12

Sequence :: Chromosome: 20; NC_000020.10 (43248163..43280376, complement)

See ADA in Epigenomics, MapViewer

Chromosome 20 - NC_000020.10 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?

ADA open form, but not the closed one, that is responsible for the functional interaction with AR and AAR.
Title: The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors.
analysis of adenosine deaminase activity in tuberculous peritonitis among patients with underlying liver cirrhosis
Title: Adenosine deaminase activity in tuberculous peritonitis among patients with underlying liver cirrhosis.
Studies report that polymorphisms in the adenosine deaminase (ADA) gene explains phenotypic variance in responses to total sleep deprivation.
Title: Heritability of performance deficit accumulation during acute sleep deprivation in twins.
The present study verified the association between the ADA G22A polymorphism and changes in sleep electroencephalogram spectral power.
Title: Adenosine deaminase polymorphism affects sleep EEG spectral power in a large epidemiological sample.
[review] Recent studies clarify the interactions of dipeptidyl peptidase IV (DPPIV) with adenosine deaminase (ADA) and the transcription transactivator Tat of human immunodeficiency virus (HIV) type-1.
Title: Molecular mechanism and structural basis of interactions of dipeptidyl peptidase IV with adenosine deaminase and human immunodeficiency virus type-1 transcription transactivator.
ADA and its isoenzymes analysis in serum of patients could be used as a useful and non-invasive diagnostic tool in evaluation of systemic lupus erythematosus active phase and the disease severity.
Title: Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern.
The new disease activity index that applies serum ADA may help in predicting disease activity in rheumatoid arthritis.
Title: Serum adenosine deaminase may predict disease activity in rheumatoid arthritis.
results indicate that the G22A polymorphism of ADA in isolation or together with HLA-B*27 is not associated with ankylosing spondylitis
Title: Lack of association of the G22A polymorphism of the ADA gene in patients with ankylosing spondylitis.
Ascitic fluid ADA measurement is helpful in the differential diagnosis of tuberculous peritonitis and peritoneal carcinomatosis.
Title: Role of ascites adenosine deaminase in differentiating between tuberculous peritonitis and peritoneal carcinomatosis.
This study demonstrated that genetic reduction of ADA activity elevates sleep pressure and plays a key role in sleep and waking quality in humans.
Title: Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans.

Submit: New GeneRIF Correction See all (91)

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

Severe combined immunodeficiency due to ADA deficiency

MIM: 102700

Genetic Testing Registry

Summary from GeneReviews: Adenosine Deaminase Deficiency

Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development and function. The phenotypic spectrum includes: Severe combined immunodeficiency disease (SCID), usually diagnosed before age six months; Less severe "delayed" onset in children between age six months and the first few years; "Late onset" in adults during the second to fourth decades; and Benign "partial ADA deficiency" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells). Infants with ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked lymphocytopenia and the absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection.

Diagnosis Testing

Diagnostic criteria for ADA deficiency are evidence of combined immunodeficiency and less than 1% of normal ADA catalytic activity in hemolysates (in un-transfused patients) or in extracts of other cells (e.g., blood mononuclear cells, fibroblasts). ADA is the only gene associated with ADA deficiency. Sequence analysis can identify most known ADA mutations, except for large deletions, which are detected by deletion/duplication analysis. Testing by both methods is available clinically.

Genetic Counseling

ADA deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if both disease-causing mutations have been identified in the family. Prenatal diagnosis for pregnancies at increased risk is also possible by analysis of ADA activity in cultured amniotic fibroblasts or cultured chorionic villi cells grown from fetal cells obtained by amniocentesis or chorionic villus sampling (CVS).

References

PMID: 20301656

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 inhibits adenosine deaminase (ADA) binding to CD26 (dipeptidyl-peptidase 4) in both CD4+ and CD4- cells; this effect requires the interaction of gp120 with CD4 or CXCR4	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P00813	P30542	ADORA1	HPRD	PubMed
P00813	P29274	ADORA2A	HPRD	PubMed
P00813	P29275	ADORA2B	HPRD	PubMed
P00813	P27487	DPP4	HPRD	PubMed
P00813	P21728	DRD1	HPRD	PubMed
P00813	P62993	GRB2	HPRD	PubMed
P00813	P04150	NR3C1	HPRD	PubMed
BioGRID:106614	BioGRID:106646	ADORA1	BioGRID	PubMed	Co-localization
BioGRID:106614	BioGRID:106647	ADORA2A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106614	BioGRID:108146	DRD1	BioGRID	PubMed	Co-localization
BioGRID:106614	BioGRID:109165	NR3C1	BioGRID	PubMed	Reconstituted Complex
BioGRID:106614	BioGRID:114523	PIAS2	BioGRID	PubMed	Two-hybrid
BioGRID:106614	BioGRID:112342	SGCD	BioGRID	PubMed	Two-hybrid
BioGRID:106614	BioGRID:119942	TERF2IP	BioGRID	PubMed	Two-hybrid
BioGRID:106614	BioGRID:117660	TINF2	BioGRID	PubMed	Two-hybrid
BioGRID:106614	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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C-MYB transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
C-MYB transcription factor network, organism-specific biosystem
C-MYB transcription factor network
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...
Primary immunodeficiency, organism-specific biosystem (from KEGG)
Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
Primary immunodeficiency, conserved biosystem (from KEGG)
Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
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 salvage, organism-specific biosystem (from REACTOME)
Purine salvage, organism-specific biosystemNucleosides and free bases generated by DNA and RNA breakdown are converted back to nucleotide monophosphates, allowing them to re-enter the pathway of purine biosynthesis. Nucleosides and free bases...
adenine and adenosine salvage III, organism-specific biosystem (from BIOCYC)
adenine and adenosine salvage III, organism-specific biosystemAdenosine nucleotides can be synthesized de novo. In that route : AMP (AMP) is synthesized via : IMP (IMP) and : ADENYLOSUCC, which is converted to AMP by the action of : ASL-MONOMER (see : PWY-6126)...
adenine and adenosine salvage III, conserved biosystem (from BIOCYC)
adenine and adenosine salvage III, conserved biosystemAdenosine nucleotides can be synthesized de novo. In that route |FRAME: AMP| (AMP) is synthesized via |FRAME: IMP| (IMP) and |FRAME: ADENYLOSUCC| , which is converted to AMP by the action of |FRAME: ...
adenosine nucleotides degradation II, organism-specific biosystem (from BIOCYC)
adenosine nucleotides degradation II, organism-specific biosystemGeneral Background The distinction between nucleoside degradation and salvage is not always straightforward. A general rule is that degradation pathways start with the nucleotide forms and convert t...
adenosine nucleotides degradation II, conserved biosystem (from BIOCYC)
adenosine nucleotides degradation II, conserved biosystemGeneral Background The distinction between nucleoside degradation and salvage is not always straight forward. A general rule is that degradation pathways start with the nucleotide forms and convert ...
purine deoxyribonucleosides degradation, organism-specific biosystem (from BIOCYC)
purine deoxyribonucleosides degradation, organism-specific biosystem
purine deoxyribonucleosides degradation
purine nucleotides degradation II (aerobic), organism-specific biosystem (from BIOCYC)
purine nucleotides degradation II (aerobic), organism-specific biosystem
purine nucleotides degradation II (aerobic)
purine nucleotides degradation II (aerobic), conserved biosystem (from BIOCYC)
purine nucleotides degradation II (aerobic), conserved biosystemGeneral Background The pathways of biosynthesis and degradation of mammalian purine and pyrimidine bases, nucleosides and nucleotides were elucidated in the 1950s and 1960s. Much work in the 1970s ...
purine ribonucleosides degradation to ribose-1-phosphate, organism-specific biosystem (from BIOCYC)
purine ribonucleosides degradation to ribose-1-phosphate, organism-specific biosystem
purine ribonucleosides degradation to ribose-1-phosphate
purine ribonucleosides degradation to ribose-1-phosphate, conserved biosystem (from BIOCYC)
purine ribonucleosides degradation to ribose-1-phosphate, conserved biosystemE. coli can use all four naturally occurring purine ribonucleosides (adenosine, guanosine, inosine and xanthosine) as total sources of carbon and energy. The first three (adenosine, guanosine, and i...

General gene information

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Markers

GDB:181143 (e-PCR)
- UniSTS:155161

GDB:181184 (e-PCR)
- UniSTS:155164

GDB:568809 (e-PCR)
- UniSTS:157757

GDB:568814 (e-PCR)
- UniSTS:157758

PMC109465P1 (e-PCR)
- UniSTS:270171

GDB:375441 (e-PCR)
- UniSTS:157024

GDB:375467 (e-PCR)
- UniSTS:157025

GDB:177907 (e-PCR)
- UniSTS:154980

GDB:178379 (e-PCR)
- UniSTS:154989

GDB:178380 (e-PCR)
- UniSTS:154990

ADA (e-PCR)
- UniSTS:480116

AL023480 (e-PCR)
- UniSTS:79022

D20S1110 (e-PCR)
- UniSTS:24021

GDB:180925 (e-PCR)
- UniSTS:155130

Genotypes

See ADA SNP Geneview Report
See ADA SNP Genotype Report
See ADA SNP Variation Viewer Report

Homology

Homologs of the ADA gene: The ADA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, S.cerevisiae, K.lactis, and S.pombe.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
adenosine deaminase activity	IDA Inferred from Direct Assay more info	PubMed
adenosine deaminase activity	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
purine nucleoside binding	IEA Inferred from Electronic Annotation more info
zinc ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
Peyer's patch development	IEA Inferred from Electronic Annotation more info
T cell activation	IDA Inferred from Direct Assay more info	PubMed
adenosine catabolic process	IDA Inferred from Direct Assay more info	PubMed
adenosine catabolic process	ISS Inferred from Sequence or Structural Similarity more info
aging	IEA Inferred from Electronic Annotation more info
cell adhesion	IEA Inferred from Electronic Annotation more info
dATP catabolic process	IEA Inferred from Electronic Annotation more info
deoxyadenosine catabolic process	IEA Inferred from Electronic Annotation more info
embryonic digestive tract development	IEA Inferred from Electronic Annotation more info
germinal center B cell differentiation	IEA Inferred from Electronic Annotation more info
histamine secretion	IEA Inferred from Electronic Annotation more info
hypoxanthine salvage	IBA Inferred from Biological aspect of Ancestor more info
inosine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
inosine biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
liver development	IEA Inferred from Electronic Annotation more info
lung alveolus development	IEA Inferred from Electronic Annotation more info
negative regulation of adenosine receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
negative regulation of circadian sleep/wake cycle, non-REM sleep	IEA Inferred from Electronic Annotation more info
negative regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
negative regulation of leukocyte migration	IEA Inferred from Electronic Annotation more info
negative regulation of mature B cell apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of mucus secretion	IEA Inferred from Electronic Annotation more info
negative regulation of penile erection	IEA Inferred from Electronic Annotation more info
negative regulation of thymocyte apoptotic process	IEA Inferred from Electronic Annotation more info
nucleobase-containing small molecule metabolic process	TAS Traceable Author Statement more info
placenta development	IEA Inferred from Electronic Annotation more info
positive regulation of B cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of T cell differentiation in thymus	IEA Inferred from Electronic Annotation more info
positive regulation of T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of alpha-beta T cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of calcium-mediated signaling	IEA Inferred from Electronic Annotation more info
positive regulation of germinal center formation	IEA Inferred from Electronic Annotation more info
positive regulation of heart rate	IEA Inferred from Electronic Annotation more info
positive regulation of smooth muscle contraction	IEA Inferred from Electronic Annotation more info
purine nucleobase metabolic process	TAS Traceable Author Statement more info
purine nucleotide salvage	IMP Inferred from Mutant Phenotype more info	PubMed
purine ribonucleoside monophosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
purine-containing compound salvage	TAS Traceable Author Statement more info
regulation of cell-cell adhesion mediated by integrin	IDA Inferred from Direct Assay more info	PubMed
response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
response to morphine	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
trophectodermal cell differentiation	IEA Inferred from Electronic Annotation more info
xanthine biosynthetic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell junction	IEA Inferred from Electronic Annotation more info
cell surface	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info
cytoplasmic membrane-bounded vesicle lumen	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
dendrite cytoplasm	IEA Inferred from Electronic Annotation more info
external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
extracellular space	IEA Inferred from Electronic Annotation more info
lysosome	IDA Inferred from Direct Assay more info	PubMed
membrane	IDA Inferred from Direct Assay more info	PubMed
neuronal cell body	IEA Inferred from Electronic Annotation more info
plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: adenosine deaminase

Names: adenosine deaminase; adenosine aminohydrolase

NP_000013.2

EC 3.5.4.4

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_007385.1 RefSeqGene

Range

5001..37214

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_16

mRNA and Protein(s)

NM_000022.2 → NP_000013.2 adenosine deaminase

Status: REVIEWED

Source sequence(s)

BC040226, BI601734

Consensus CDS

CCDS13335.1

UniProtKB/Swiss-Prot

P00813

Related

ENSP00000361965, OTTHUMP00000031785, ENST00000372874, OTTHUMT00000080509

Conserved Domains (2) summary

cd01320
Location:8 – 347
Blast Score: 960

ADA; Adenosine deaminase (ADA) is a monomeric zinc dependent enzyme which catalyzes the irreversible hydrolytic deamination of both adenosine, as well as desoxyadenosine, to ammonia and inosine or desoxyinosine, respectively. ADA plays an important role in ...

COG1816
Location:9 – 350
Blast Score: 505

Add; Adenosine deaminase [Nucleotide transport and metabolism]

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_000020.10 Reference GRCh37.p10 Primary Assembly

Range

43248163..43280376, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000152.1 Alternate HuRef

Range

39989704..40021872, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018931.1 Alternate CHM1_1.0

Range

43218892..43251107, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01052645.1 (7111..31639)	None
genomic	ABBA01052646.1	None
genomic	AL139352.16 (101..21033)	None
genomic	AMYH01011934.1 (87680..119895)	None
genomic	CH471077.2	EAW75904.1
		EAW75905.1
		EAW75906.1
		EAW75907.1
genomic	HH769637.1	CBX85542.1
genomic	HH769781.1	CBX85614.1
genomic	M13792.1	AAA78791.1
genomic	X02189.1	CAA26130.1
genomic	X02190.1	None
genomic	Z97053.2 (136428..147708)	None
mRNA	AK123988.1	None
mRNA	AK223397.1	BAD97117.1
mRNA	AL832305.1	None
mRNA	BC007678.2	AAH07678.1
mRNA	BC040226.1	AAH40226.1
mRNA	BI601734.1	None
mRNA	X02994.1	CAA26734.1
other-genetic	DQ892681.2	ABM83607.1
other-genetic	DQ895924.2	ABM86850.1