ADA

Protein identityUniProt · HPA

UniProt accession

P00813

Gene

ADA

Ensembl

ENSG00000196839

Chromosome

20

Canonical length

363 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

363 residues, UniProt reviewed canonical sequence.

>P00813|ADA
     1  MAQTPAFDKP KVELHVHLDG SIKPETILYY GRRRGIALPA NTAEGLLNVI GMDKPLTLPD
    61  FLAKFDYYMP AIAGCREAIK RIAYEFVEMK AKEGVVYVEV RYSPHLLANS KVEPIPWNQA
   121  EGDLTPDEVV ALVGQGLQEG ERDFGVKARS ILCCMRHQPN WSPKVVELCK KYQQQTVVAI
   181  DLAGDETIPG SSLLPGHVQA YQEAVKSGIH RTVHAGEVGS AEVVKEAVDI LKTERLGHGY
   241  HTLEDQALYN RLRQENMHFE ICPWSSYLTG AWKPDTEHAV IRLKNDQANY SLNTDDPLIF
   301  KSTLDTDYQM TKRDMGFTEE EFKRLNINAA KSSFLPEDEK RELLDLLYKA YGMPPSASAG
   361  QNL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADA 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.21

Highest tissue expression

454 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADA.

Disease | AllUniProt

Conditions ADA is implicated in, by any mechanism.

• Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) MIM:102700

Disease | GeneticClinVar

165 pathogenic / likely-pathogenic of 764 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
• Severe combined immunodeficiency disease
• ADA-related disorder
• SCID due to ADA deficiency, delayed onset
• Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive

ReferencesPubMed · IEDB

Publications for ADA 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)

1.32

gnomAD pLI

0

gnomAD missense Z

0.12

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenosine catabolic process
• adenosine metabolic process
• allantoin metabolic process
• alpha-beta T cell differentiation
• amide catabolic process
• AMP catabolic process
• AMP salvage
• B cell proliferation
• calcium-mediated signaling
• cell adhesion
• dAMP catabolic process
• dATP catabolic process
• deoxyadenosine catabolic process
• embryonic digestive tract development
• germinal center B cell differentiation
• germinal center formation
• GMP salvage
• hypoxanthine salvage
• inosine biosynthetic process
• leukocyte migration
• liver development
• lung alveolus development
• mucus secretion
• negative regulation of inflammatory response
• negative regulation of leukocyte migration
• negative regulation of mature B cell apoptotic process
• negative regulation of mucus secretion
• negative regulation of thymocyte apoptotic process
• penile erection
• Peyer's patch development
• placenta development
• positive regulation of alpha-beta T cell differentiation
• positive regulation of B cell proliferation
• positive regulation of calcium-mediated signaling
• positive regulation of germinal center formation
• positive regulation of heart rate
• positive regulation of smooth muscle contraction
• positive regulation of T cell differentiation in thymus
• positive regulation of T cell receptor signaling pathway
• purine-containing compound salvage
• regulation of cell-cell adhesion mediated by integrin
• regulation of circadian sleep/wake cycle, sleep
• response to hypoxia
• response to purine-containing compound
• smooth muscle contraction
• T cell activation
• T cell differentiation in thymus
• T cell receptor signaling pathway
• thymocyte apoptotic process
• trophectodermal cell differentiation
• xenobiotic metabolic process
• mature B cell apoptotic process
• negative regulation of adenosine receptor signaling pathway
• negative regulation of penile erection
• purine nucleotide salvage
• xanthine biosynthetic process

Molecular functions

• adenosine deaminase activity
• deaminase activity
• zinc ion binding
• 2'-deoxyadenosine deaminase activity

Cellular components

• anchoring junction
• cell surface
• cytoplasmic vesicle lumen
• cytosol
• external side of plasma membrane
• lysosome
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Adenosine deaminase domain
• Adenosine/adenine deaminase
• Adenosine/AMP deaminase active site
• Metal-dependent hydrolase
• Adenosine deaminase
• Adenosine deaminase

KeywordsUniProt

• Acetylation
• Cell adhesion
• Cell junction
• Cell membrane
• Cytoplasm
• Cytoplasmic vesicle
• Hereditary hemolytic anemia
• Hydrolase
• Lysosome
• Membrane
• Metal-binding
• Nucleotide metabolism
• SCID
• Zinc

InteractionsUniProt · HPA

Protein binding partners of ADA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DPP4
• PLG