Human Gene ADA (ENST00000372874.9) from GENCODE V44
  Description: Homo sapiens adenosine deaminase (ADA), transcript variant 1, mRNA. (from RefSeq NM_000022)
RefSeq Summary (NM_000022): This gene encodes an enzyme that catalyzes the hydrolysis of adenosine to inosine in the purine catabolic pathway. Various mutations have been described for this gene and have been linked to human diseases related to impaired immune function such as severe combined immunodeficiency disease (SCID) which is the result of a deficiency in the ADA enzyme. In ADA-deficient individuals there is a marked depletion of T, B, and NK lymphocytes, and consequently, a lack of both humoral and cellular immunity. Conversely, elevated levels of this enzyme are associated with congenital hemolytic anemia. [provided by RefSeq, Sep 2019].
Gencode Transcript: ENST00000372874.9
Gencode Gene: ENSG00000196839.14
Transcript (Including UTRs)
   Position: hg38 chr20:44,619,522-44,651,699 Size: 32,178 Total Exon Count: 12 Strand: -
Coding Region
   Position: hg38 chr20:44,619,834-44,651,607 Size: 31,774 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:44,619,522-44,651,699)mRNA (may differ from genome)Protein (363 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ADA_HUMAN
DESCRIPTION: RecName: Full=Adenosine deaminase; EC=3.5.4.4; AltName: Full=Adenosine aminohydrolase;
FUNCTION: Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte- epithelial cell adhesion.
CATALYTIC ACTIVITY: Adenosine + H(2)O = inosine + NH(3).
COFACTOR: Binds 1 zinc ion per subunit.
SUBUNIT: Interacts with DPP4 (extracellular domain).
SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Extracellular side. Cell junction. Cytoplasmic vesicle lumen (By similarity). Cytoplasm (By similarity). Note=Colocalized with DPP4 at the cell junction in lymphocyte-epithelial cell adhesion.
TISSUE SPECIFICITY: Found in all tissues, occurs in large amounts in T-lymphocytes and, at the time of weaning, in gastrointestinal tissues.
POLYMORPHISM: There is a common allele, ADA*2, also known as the ADA 2 allozyme. It is associated with the reduced metabolism of adenosine to inosine. It specifically enhances deep sleep and slow-wave activity (SWA) during sleep.
DISEASE: Defects in ADA are the cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) [MIM:102700]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA-SCID is an autosomal recessive form accounting for about 50% of non-X-linked SCIDs. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.
SIMILARITY: Belongs to the adenosine and AMP deaminases family.
WEB RESOURCE: Name=ADAbase; Note=ADA mutation db; URL="http://bioinf.uta.fi/ADAbase/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ADA";
WEB RESOURCE: Name=Wikipedia; Note=Adenosine deaminase entry; URL="http://en.wikipedia.org/wiki/Adenosine_deaminase";
WEB RESOURCE: Name=Mendelian genes adenosine deaminase (ADA); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/ADA";

-  Primer design for this transcript
 

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Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: ADA
Diseases sorted by gene-association score: severe combined immunodeficiency due to ada deficiency* (1550), adenosine deaminase deficiency* (562), omenn syndrome* (140), pleural tuberculosis (38), tuberculous peritonitis (36), pleurisy (36), severe combined immunodeficiency (35), extrapulmonary tuberculosis (31), pericardial effusion (29), pleural disease (29), tuberculous meningitis (28), pericardial tuberculosis (26), dyschromatosis symmetrica hereditaria (26), pleural empyema (22), tuberculous empyema (20), severe combined immune deficiency (18), listeria meningitis (18), cutaneous anthrax (18), pericarditis (16), cryptococcal meningitis (16), pulmonary tuberculosis (16), meningitis (14), constrictive pericarditis (13), gastrointestinal tuberculosis (12), reticular dysgenesis (12), alk-negative anaplastic large cell lymphoma (11), hairy cell leukemia (10), abdominal tuberculosis (10), prolymphocytic leukemia (9), peritonitis (9), severe combined immunodeficiency, x-linked (8), miliary tuberculosis (8), streptococcal meningitis (6), combined t cell and b cell immunodeficiency (6), chickenpox (6), viral meningitis (6), primary immunodeficiency disease (5), gaucher disease, type i (5), early onset absence epilepsy (5), poikiloderma with neutropenia (5), congenital hemolytic anemia (5), pigmentation disease (5), tuberculosis (4), asthma (4), acquired immunodeficiency syndrome (2), maturity-onset diabetes of the young (2), sarcoidosis 1 (2), chronic lymphocytic leukemia (2), primary bacterial infectious disease (1), behcet syndrome (1), amyotrophic lateral sclerosis 1 (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 33.60 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 219.69 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -35.6092-0.387 Picture PostScript Text
3' UTR -88.20312-0.283 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006650 - A/AMP_deam_AS
IPR001365 - A/AMP_deaminase_dom
IPR006330 - Ado/ade_deaminase

Pfam Domains:
PF00962 - Adenosine/AMP deaminase

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1M7M - Model 3IAR - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P00813
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
MGIRGD   SGD
Protein SequenceProtein Sequence   Protein Sequence
AlignmentAlignment   Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001883 purine nucleoside binding
GO:0004000 adenosine deaminase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0019239 deaminase activity
GO:0046872 metal ion binding

Biological Process:
GO:0001666 response to hypoxia
GO:0001701 in utero embryonic development
GO:0001821 histamine secretion
GO:0001829 trophectodermal cell differentiation
GO:0001889 liver development
GO:0001890 placenta development
GO:0002314 germinal center B cell differentiation
GO:0002636 positive regulation of germinal center formation
GO:0002686 negative regulation of leukocyte migration
GO:0002906 negative regulation of mature B cell apoptotic process
GO:0006154 adenosine catabolic process
GO:0006157 deoxyadenosine catabolic process
GO:0007155 cell adhesion
GO:0007568 aging
GO:0009117 nucleotide metabolic process
GO:0009168 purine ribonucleoside monophosphate biosynthetic process
GO:0010460 positive regulation of heart rate
GO:0030324 lung development
GO:0030890 positive regulation of B cell proliferation
GO:0032261 purine nucleotide salvage
GO:0033089 positive regulation of T cell differentiation in thymus
GO:0033197 response to vitamin E
GO:0033632 regulation of cell-cell adhesion mediated by integrin
GO:0042110 T cell activation
GO:0042323 negative regulation of circadian sleep/wake cycle, non-REM sleep
GO:0042493 response to drug
GO:0042542 response to hydrogen peroxide
GO:0043066 negative regulation of apoptotic process
GO:0043101 purine-containing compound salvage
GO:0043103 hypoxanthine salvage
GO:0043278 response to morphine
GO:0045187 regulation of circadian sleep/wake cycle, sleep
GO:0045580 regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0045987 positive regulation of smooth muscle contraction
GO:0046061 dATP catabolic process
GO:0046085 adenosine metabolic process
GO:0046101 hypoxanthine biosynthetic process
GO:0046103 inosine biosynthetic process
GO:0046111 xanthine biosynthetic process
GO:0046638 positive regulation of alpha-beta T cell differentiation
GO:0048286 lung alveolus development
GO:0048541 Peyer's patch development
GO:0048566 embryonic digestive tract development
GO:0050728 negative regulation of inflammatory response
GO:0050850 positive regulation of calcium-mediated signaling
GO:0050862 positive regulation of T cell receptor signaling pathway
GO:0050870 positive regulation of T cell activation
GO:0060169 negative regulation of adenosine receptor signaling pathway
GO:0060407 negative regulation of penile erection
GO:0070244 negative regulation of thymocyte apoptotic process
GO:0070256 negative regulation of mucus secretion

Cellular Component:
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0009897 external side of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0030054 cell junction
GO:0031410 cytoplasmic vesicle
GO:0032839 dendrite cytoplasm
GO:0043025 neuronal cell body
GO:0060205 cytoplasmic vesicle lumen


-  Descriptions from all associated GenBank mRNAs
  AL832305 - Homo sapiens mRNA; cDNA DKFZp667G2419 (from clone DKFZp667G2419).
BC007678 - Homo sapiens adenosine deaminase, mRNA (cDNA clone MGC:3971 IMAGE:3629376), complete cds.
BC040226 - Homo sapiens adenosine deaminase, mRNA (cDNA clone MGC:34825 IMAGE:5198265), complete cds.
AK123988 - Homo sapiens cDNA FLJ41994 fis, clone SPLEN2028844.
X02994 - Human mRNA for adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4).
JD112553 - Sequence 93577 from Patent EP1572962.
JD476190 - Sequence 457214 from Patent EP1572962.
AK223397 - Homo sapiens mRNA for adenosine deaminase variant, clone: FCC107E03.
JD120796 - Sequence 101820 from Patent EP1572962.
JD150318 - Sequence 131342 from Patent EP1572962.
KJ890629 - Synthetic construct Homo sapiens clone ccsbBroadEn_00023 ADA gene, encodes complete protein.
KR710023 - Synthetic construct Homo sapiens clone CCSBHm_00008997 ADA (ADA) mRNA, encodes complete protein.
KR710024 - Synthetic construct Homo sapiens clone CCSBHm_00009001 ADA (ADA) mRNA, encodes complete protein.
KR710025 - Synthetic construct Homo sapiens clone CCSBHm_00009019 ADA (ADA) mRNA, encodes complete protein.
KR710026 - Synthetic construct Homo sapiens clone CCSBHm_00009032 ADA (ADA) mRNA, encodes complete protein.
DQ892681 - Synthetic construct clone IMAGE:100005311; FLH188810.01X; RZPDo839G0473D adenosine deaminase (ADA) gene, encodes complete protein.
DQ895924 - Synthetic construct Homo sapiens clone IMAGE:100010384; FLH188806.01L; RZPDo839G0463D adenosine deaminase (ADA) gene, encodes complete protein.
KJ534760 - Homo sapiens clone ADA_iso-A_adult-A03 adenosine deaminase isoform A (ADA) mRNA, partial cds, alternatively spliced.
KU177892 - Homo sapiens adenosine deaminase isoform 1 (ADA) mRNA, partial cds.
KU177893 - Homo sapiens adenosine deaminase isoform 2 (ADA) mRNA, partial cds, alternatively spliced.
KU177894 - Homo sapiens adenosine deaminase isoform 3 (ADA) mRNA, partial cds, alternatively spliced.
KU177895 - Homo sapiens adenosine deaminase isoform 4 (ADA) mRNA, partial cds, alternatively spliced.
AB528992 - Synthetic construct DNA, clone: pF1KE0927, Homo sapiens ADA gene for adenosine deaminase, without stop codon, in Flexi system.
JD116082 - Sequence 97106 from Patent EP1572962.
JD103651 - Sequence 84675 from Patent EP1572962.
JD443979 - Sequence 425003 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00230 - Purine metabolism
hsa01100 - Metabolic pathways
hsa05340 - Primary immunodeficiency

BioCyc Knowledge Library
PWY-6353 - purine nucleotides degradation
PWY-6609 - adenine and adenosine salvage III
PWY-7179-1 - purine deoxyribonucleosides degradation
PWY0-1296 - purine ribonucleosides degradation to ribose-1-phosphate
PWY66-409 - superpathway of purine nucleotide salvage
SALVADEHYPOX-PWY - adenosine nucleotides degradation

Reactome (by CSHL, EBI, and GO)

Protein P00813 (Reactome details) participates in the following event(s):

R-HSA-74241 (2'-deoxy)adenosine + H2O => (2'-deoxy)inosine + NH4+ (ADA)
R-HSA-74217 Purine salvage
R-HSA-8956321 Nucleotide salvage
R-HSA-15869 Metabolism of nucleotides
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ADA1, ADA_HUMAN, ENST00000372874.1, ENST00000372874.2, ENST00000372874.3, ENST00000372874.4, ENST00000372874.5, ENST00000372874.6, ENST00000372874.7, ENST00000372874.8, NM_000022, P00813, Q53F92, Q6LA59, uc002xmj.1, uc002xmj.2, uc002xmj.3, uc002xmj.4, uc002xmj.5
UCSC ID: ENST00000372874.9
RefSeq Accession: NM_000022
Protein: P00813 (aka ADA_HUMAN)
CCDS: CCDS13335.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ADA:
ada (Adenosine Deaminase Deficiency)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.