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Reviewed, UniProtKB/Swiss-Prot P00813 (ADA_HUMAN)

Last modified July 7, 2009. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Adenosine deaminase
    EC=3.5.4.4
Alternative name(s):
    Adenosine aminohydrolase
Gene names
Name: ADA
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length363 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

Adenosine + H2O = inosine + NH3.

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.

Involvement in 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. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22

In hereditary hemolytic anemia, the level of this enzyme in erythrocytes increases 50-70 times.

Sequence similarities

Belongs to the adenosine and AMP deaminases family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 363362Adenosine deaminase
PRO_0000194352

Sites

Active site2141 Potential
Active site2621 Potential
Active site2951 Potential
Active site2961 Potential

Amino acid modifications

Modified residue21N-acetylalanine Ref.8

Natural variations

Natural variant81D → N in allele ADA*2; in about 10% of the population; 20% to 30% decrease in activity; affects duration and intensity of deep sleep. Ref.11 Ref.23
VAR_002209
Natural variant151H → D in ADASCID; loss of activity. Ref.20
VAR_002210
Natural variant201G → R in ADASCID; loss of activity. Ref.18
VAR_002211
Natural variant741G → C in ADASCID; delayed-onset. Ref.22
VAR_002212
Natural variant761R → W in ADASCID.
VAR_002213
Natural variant801K → R Ref.19 Ref.23
VAR_002214
Natural variant831A → D in ADASCID; loss of activity. Ref.20
VAR_002215
Natural variant1011R → L in ADASCID. Ref.13 Ref.14 Ref.17
VAR_002216
Natural variant1011R → Q in ADASCID; loss of activity. Ref.13 Ref.14 Ref.17
VAR_002218
Natural variant1011R → W in ADASCID. Ref.13 Ref.14 Ref.17
VAR_002217
Natural variant1071L → P in ADASCID.
VAR_002219
Natural variant1291V → M in ADASCID; delayed-onset. Ref.22
VAR_002220
Natural variant1401G → E in ADASCID. Ref.22
VAR_002221
Natural variant1421R → Q in ADASCID; 20% of activity; ADA deficiency of late onset. Ref.19
VAR_002222
Natural variant1491R → Q in ADASCID. Ref.22
VAR_002223
Natural variant1491R → W in ADASCID. Ref.22
VAR_002224
Natural variant1521L → M in ADASCID; 1,5% of activity, partial ADA deficiency. Ref.21
VAR_002225
Natural variant1561R → C in ADASCID. Ref.16 Ref.17
VAR_002226
Natural variant1561R → H in ADASCID. Ref.16 Ref.17
VAR_002227
Natural variant1771V → M in ADASCID; loss of activity. Ref.17
VAR_002228
Natural variant1791A → D in ADASCID; loss of activity. Ref.20
VAR_002229
Natural variant1991Q → P in ADASCID; delayed-onset. Ref.22
VAR_002230
Natural variant2111R → C in ADASCID; late onset. Ref.14
VAR_002231
Natural variant2111R → H in ADASCID. Ref.14
VAR_002232
Natural variant2151A → T in ADASCID.
VAR_002233
Natural variant2161G → R in ADASCID; severe.
VAR_002234
Natural variant2331T → I in ADASCID; 20% of activity, partial ADA deficiency. Ref.21
VAR_002235
Natural variant2741P → L in ADASCID.
VAR_002236
Natural variant2911S → L in ADASCID. Ref.16
VAR_002237
Natural variant2971P → Q in ADASCID. Ref.15
VAR_002238
Natural variant3041L → R in ADASCID; loss of activity.
VAR_002239
Natural variant3291A → V in ADASCID. Ref.14
VAR_002240
Natural variant3371Missing in ADASCID.
VAR_002241

Experimental info

Sequence conflict3401K → R in BAD97117. Ref.5

Secondary structure

............................................................ 363
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00813-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 786BC5085CA9AFCB

FASTA36340,764
        10         20         30         40         50         60 
MAQTPAFDKP KVELHVHLDG SIKPETILYY GRRRGIALPA NTAEGLLNVI GMDKPLTLPD 

        70         80         90        100        110        120 
FLAKFDYYMP AIAGCREAIK RIAYEFVEMK AKEGVVYVEV RYSPHLLANS KVEPIPWNQA 

       130        140        150        160        170        180 
EGDLTPDEVV ALVGQGLQEG ERDFGVKARS ILCCMRHQPN WSPKVVELCK KYQQQTVVAI 

       190        200        210        220        230        240 
DLAGDETIPG SSLLPGHVQA YQEAVKSGIH RTVHAGEVGS AEVVKEAVDI LKTERLGHGY 

       250        260        270        280        290        300 
HTLEDQALYN RLRQENMHFE ICPWSSYLTG AWKPDTEHAV IRLKNDQANY SLNTDDPLIF 

       310        320        330        340        350        360 
KSTLDTDYQM TKRDMGFTEE EFKRLNINAA KSSFLPEDEK RELLDLLYKA YGMPPSASAG 


QNL 

« Hide

References

« Hide 'large scale' references
[1]"Human adenosine deaminase. cDNA and complete primary amino acid sequence."
Daddona P.E., Shewach D.S., Kelley W.N., Argos P., Markham A.F., Orkin S.H.
J. Biol. Chem. 259:12101-12106(1984) [PubMed: 6090454] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Sequence of human adenosine deaminase cDNA including the coding region and a small intron."
Wiginton D.A., Adrian G.S., Hutton J.J.
Nucleic Acids Res. 12:2439-2446(1984) [PubMed: 6546794] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Adenosine deaminase: characterization and expression of a gene with a remarkable promoter."
Valerio D., Duyvesteyn M.G.C., Dekker B.M.M., Weeda G., Berkvens T.M., van der Voorn L., van Ormondt H., van der Eb A.J.
EMBO J. 4:437-443(1985) [PubMed: 3839456] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequence and structure of the gene for human adenosine deaminase."
Wiginton D.A., Kaplan D.J., States J.C., Akeson A.L., Perme C.M., Bilyk I.J., Vaughn A.J., Lattier D.L., Hutton J.J.
Biochemistry 25:8234-8244(1986) [PubMed: 3028473] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thymus.
[6]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed: 11780052] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Placenta.
[8]Bienvenut W.V.
Submitted (AUG-2004) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-11, ACETYLATION AT ALA-2, MASS SPECTROMETRY.
Tissue: B-cell lymphoma.
[9]"Molecular cloning of human adenosine deaminase gene sequences."
Orkin S.H., Daddona P.E., Shewach D.S., Markham A.F., Bruns G.A., Goff S.C., Kelley W.N.
J. Biol. Chem. 258:12753-12756(1983) [PubMed: 6688808] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 141-363.
[10]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]"An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover."
Hirschhorn R., Yang D.R., Israni A.
Ann. Hum. Genet. 58:1-9(1994) [PubMed: 8031011] [Abstract]
Cited for: VARIANT ADA*2 ASN-8.
[12]"Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines."
Adrian G.S., Wiginton D.A., Hutton J.
Mol. Cell. Biol. 4:1712-1717(1984) [PubMed: 6208479] [Abstract]
Cited for: VARIANTS ADASCID.
[13]"Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency."
Bonthron D.T., Markham A.F., Ginsburg D., Orkin S.H.
J. Clin. Invest. 76:894-897(1985) [PubMed: 3839802] [Abstract]
Cited for: VARIANT ADASCID GLN-101.
[14]"Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts."
Akeson A.L., Wiginton D.A., Dusing M.R., States J.C., Hutton J.J.
J. Biol. Chem. 263:16291-16296(1988) [PubMed: 3182793] [Abstract]
Cited for: VARIANTS ADASCID TRP-101; HIS-211 AND VAL-329.
[15]"Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency."
Hirschhorn R., Tzall S., Ellenbogen A., Orkin S.H.
J. Clin. Invest. 83:497-501(1989) [PubMed: 2783588] [Abstract]
Cited for: VARIANT ADASCID GLN-297.
[16]"Identification of two new missense mutations (R156C and S291L) in two ADA-SCID patients unusual for response to therapy with partial exchange transfusions."
Hirschhorn R.
Hum. Mutat. 1:166-168(1992) [PubMed: 1284479] [Abstract]
Cited for: VARIANTS ADASCID CYS-156 AND LEU-291.
[17]"Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype."
Santisteban I., Arredondo-Vega F.X., Kelly S., Mary A., Fischer A., Hummell D.S., Lawton A., Sorensen R.U., Stiehm E.R., Uribe L., Weinberg K., Hershfield M.S.
J. Clin. Invest. 92:2291-2302(1993) [PubMed: 8227344] [Abstract]
Cited for: VARIANTS ADASCID LEU-101; HIS-156 AND MET-177.
[18]"Homozygosity for a missense mutation (G20R) associated with neonatal onset adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID)."
Yang D.R., Huie M.L., Hirschhorn R.
Clin. Immunol. Immunopathol. 70:171-175(1994) [PubMed: 8299233] [Abstract]
Cited for: VARIANT ADASCID ARG-20.
[19]"Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA."
Santisteban I., Arredondo-Vega F.X., Kelly S., Loubser M., Meydan N., Roifman C., Howell P.L., Bowen T., Weinberg K.I., Schroeder M.L., Hershfield M.S.
Hum. Mol. Genet. 4:2081-2087(1995) [PubMed: 8589684] [Abstract]
Cited for: VARIANT ADASCID GLN-142, VARIANT ARG-80.
[20]"Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site."
Santisteban I., Arredondo-Vega F.X., Kelly S., Debre M., Fisher A., Perignon J.L., Hilman B., Eldahr J., Dreyfus D.H., Gelfand E.W., Howell P.L., Hershfield M.S.
Hum. Mutat. 5:243-250(1995) [PubMed: 7599635] [Abstract]
Cited for: VARIANTS ADASCID ASP-15; ASP-83 AND ASP-179.
[21]"Two newly identified mutations (Thr233Ile and Leu152Met) in partially adenosine deaminase-deficient (ADA-) individuals that result in differing biochemical and metabolic phenotypes."
Hirschhorn R., Borkowsky W., Jiang C.-K., Yang D.R., Jenkins T.
Hum. Genet. 100:22-29(1997) [PubMed: 9225964] [Abstract]
Cited for: VARIANTS ADASCID MET-152 AND ILE-233.
[22]"Seven novel mutations in the adenosine deaminase (ADA)gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del."
Arredondo-Vega F.X., Santisteban I., Notarangelo L.D., el Dahr J., Buckley R., Roifman C., Conley M.E., Hershfield M.S.
Hum. Mutat. 11:482-482(1998)
Cited for: VARIANTS ADASCID CYS-74; MET-129; GLU-140; TRP-149 AND PRO-199.
[23]"A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans."
Retey J.V., Adam M., Honegger E., Khatami R., Luhmann U.F.O., Jung H.H., Berger W., Landolt H.-P.
Proc. Natl. Acad. Sci. U.S.A. 102:15676-15681(2005) [PubMed: 16221767] [Abstract]
Cited for: EFFECT OF VARIANT ADA*2 ASN-8 ON SLEEP.
+Additional computationally mapped references.

Web resources

ADAbase

ADA mutation db

GeneReviews
Wikipedia

Adenosine deaminase entry

Cross-references

Sequence databases

X02994 mRNA. Translation: CAA26734.1.
X02189 expand/collapse EMBL AC list , X02190, X02191, X02192, X02193, X02194, X02195, X02196, X02197, X02198, X02199 Genomic DNA. Translation: CAA26130.1. Sequence problems.
M13792 Genomic DNA. Translation: AAA78791.1.
AL139352, Z97053 Genomic DNA. Translation: CAH73885.1.
Z97053, AL139352 Genomic DNA. Translation: CAB09782.2.
AK223397 mRNA. Translation: BAD97117.1.
BC007678 mRNA. Translation: AAH07678.1.
BC040226 mRNA. Translation: AAH40226.1.
IPIIPI00296441.
PIRDUHUA. A91032.
RefSeqNP_000013.2.
UniGeneHs.654536

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1M7Mmodel-A1-363[»]
SMRP00813. Positions 3-350, 4-351.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:371N.

PTM databases

PhosphoSiteP00813.

2-D gel databases

Aarhus/Ghent-2DPAGE5305. IEF.

Proteomic databases

PeptideAtlasP00813.
PRIDEP00813.

Genome annotation databases

EnsemblENSG00000196839. Homo sapiens. [Contig view]
GeneID100.
KEGGhsa:100.
UCSCuc002xmj.1. human.

Organism-specific databases

GeneCardsGC20M042681.
H-InvDBHIX0015842.
HGNCHGNC:186. ADA.
HPACAB004307.
HPA001399.
MIM102700. phenotype.
608958. gene.
Orphanet277. Severe combined immunodeficiency due to adenosine deaminase deficiency.
PharmGKBPA24503.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP00813.
HOVERGENP00813.

Enzyme and pathway databases

BRENDA3.5.4.4. 247.
ReactomeREACT_1698. Metablism of nucleotides.

Gene expression databases

ArrayExpressP00813.
BgeeP00813.
CleanExHS_ADA.
GermOnlineENSG00000196839. Homo sapiens.

Family and domain databases

InterProIPR006650. A/AMP_deam_AS.
IPR001365. A/AMP_deaminase.
IPR006330. A_deaminase.
[Graphical view]
PANTHERPTHR11409. A/AMP_deaminase. 1 hit.
PfamPF00962. A_deaminase. 1 hit.
[Graphical view]
TIGRFAMsTIGR01430. aden_deam. 1 hit.
PROSITEPS00485. A_DEAMINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

BindingDBP00813.
DrugBankDB00640. Adenosine.
DB00242. Cladribine.
DB00975. Dipyridamole.
DB00199. Erythromycin.
DB01073. Fludarabine.
DB00249. Idoxuridine.
DB01280. Nelarabine.
DB00552. Pentostatin.
DB00277. Theophylline.
DB00194. Vidarabine.
NextBio377.
SOURCESearch...

Entry information

Entry nameADA_HUMAN
AccessionPrimary (citable) accession number: P00813
Secondary accession number(s): Q53F92, Q6LA59
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: July 7, 2009
This is version 123 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents