P00813 (ADA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenosine deaminase
EC=3.5.4.4

Alternative name(s):
Adenosine aminohydrolase

Gene names

Name:	ADA
Synonyms:	ADA1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	363 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.13
Catalytic activity	Adenosine + H2O = inosine + NH3.
Cofactor	Binds 1 zinc ion per subunit. Ref.18
Subunit structure	Interacts with DPP4 (extracellular domain). Ref.10 Ref.11 Ref.12 Ref.14
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. Ref.10 Ref.13
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	Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) [MIM:102700]: An autosomal recessive disorder accounting for about 50% of non-X-linked SCIDs. 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 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.29 Ref.31
Sequence similarities	Belongs to the adenosine and AMP deaminases family.

Ontologies

Keywords
Biological process	Cell adhesion Nucleotide metabolism
Cellular component	Cell junction Cell membrane Cytoplasm Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary hemolytic anemia SCID
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Peyer's patch development Inferred from electronic annotation. Source: Compara T cell activation Inferred from direct assay PubMed 7594462. Source: UniProtKB adenosine catabolic process Inferred from direct assay PubMed 16670267. Source: UniProtKB aging Inferred from electronic annotation. Source: Compara cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW dATP catabolic process Inferred from electronic annotation. Source: Compara deoxyadenosine catabolic process Inferred from electronic annotation. Source: Compara embryonic digestive tract development Inferred from electronic annotation. Source: Compara germinal center B cell differentiation Inferred from electronic annotation. Source: Compara histamine secretion Inferred from electronic annotation. Source: Compara hypoxanthine salvage Inferred from Biological aspect of Ancestor. Source: RefGenome inosine biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB liver development Inferred from electronic annotation. Source: Compara lung alveolus development Inferred from electronic annotation. Source: Compara negative regulation of adenosine receptor signaling pathway Inferred from direct assay PubMed 16670267. Source: UniProtKB negative regulation of circadian sleep/wake cycle, non-REM sleep Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of leukocyte migration Inferred from electronic annotation. Source: Compara negative regulation of mature B cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of mucus secretion Inferred from electronic annotation. Source: Compara negative regulation of penile erection Inferred from electronic annotation. Source: Compara negative regulation of thymocyte apoptotic process Inferred from electronic annotation. Source: Compara placenta development Inferred from electronic annotation. Source: Compara positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of T cell differentiation in thymus Inferred from electronic annotation. Source: Compara positive regulation of T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of alpha-beta T cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of calcium-mediated signaling Inferred from electronic annotation. Source: Compara positive regulation of germinal center formation Inferred from electronic annotation. Source: Compara positive regulation of heart rate Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle contraction Inferred from electronic annotation. Source: Compara purine nucleotide salvage Inferred from mutant phenotype PubMed 9361033. Source: UniProtKB purine ribonucleoside monophosphate biosynthetic process Inferred from electronic annotation. Source: InterPro regulation of cell-cell adhesion mediated by integrin Inferred from direct assay Ref.13. Source: UniProtKB response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from direct assay PubMed 16670267. Source: UniProtKB response to morphine Inferred from electronic annotation. Source: Compara trophectodermal cell differentiation Inferred from electronic annotation. Source: Compara xanthine biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic membrane-bounded vesicle lumen Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome dendrite cytoplasm Inferred from electronic annotation. Source: Compara external side of plasma membrane Inferred from direct assay PubMed 16670267PubMed 7759315. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: Compara lysosome Inferred from direct assay PubMed 8452534. Source: UniProtKB neuronal cell body Inferred from electronic annotation. Source: Compara
Molecular_function	adenosine deaminase activity Inferred from direct assay PubMed 11999881PubMed 16670267Ref.23PubMed 8452534PubMed 9361033. Source: UniProtKB purine nucleoside binding Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from mutant phenotype Ref.29. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 363

362

Adenosine deaminase

PRO_0000194352

Sites

Active site

217

1

Proton donor Probable

Metal binding

15

1

Zinc; catalytic

Metal binding

17

1

Zinc; catalytic

Metal binding

214

1

Zinc; catalytic

Metal binding

295

1

Zinc; catalytic

Binding site

17

1

Substrate

Binding site

19

1

Substrate

Binding site

184

1

Substrate; via amide nitrogen

Binding site

296

1

Substrate

Site

238

1

Important for catalytic activity By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

54

1

N6-acetyllysine Ref.16

Modified residue

232

1

N6-acetyllysine Ref.16

Natural variations

Natural variant

8

1

D → 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.20 Ref.32

VAR_002209

Natural variant

15

1

H → D in ADASCID; loss of activity. Ref.29
Corresponds to variant rs121908725 [ dbSNP | Ensembl ].

VAR_002210

Natural variant

20

1

G → R in ADASCID; loss of activity. Ref.27
Corresponds to variant rs121908724 [ dbSNP | Ensembl ].

VAR_002211

Natural variant

74

1

G → C in ADASCID; delayed-onset. Ref.31
Corresponds to variant rs121908730 [ dbSNP | Ensembl ].

VAR_002212

Natural variant

76

1

R → W in ADASCID. Ref.19
Corresponds to variant rs121908736 [ dbSNP | Ensembl ].

VAR_002213

Natural variant

80

1

K → R. Ref.28
Corresponds to variant rs11555566 [ dbSNP | Ensembl ].

VAR_002214

Natural variant

83

1

A → D in ADASCID; loss of activity. Ref.29
Corresponds to variant rs121908726 [ dbSNP | Ensembl ].

VAR_002215

Natural variant

101

1

R → L in ADASCID. Ref.26
Corresponds to variant rs121908720 [ dbSNP | Ensembl ].

VAR_002216

Natural variant

101

1

R → Q in ADASCID; loss of activity. Ref.22
Corresponds to variant rs28930970 [ dbSNP | Ensembl ].

VAR_002218

Natural variant

101

1

R → W in ADASCID. Ref.23
Corresponds to variant rs28930969 [ dbSNP | Ensembl ].

VAR_002217

Natural variant

107

1

L → P in ADASCID. Ref.19
Corresponds to variant rs121908739 [ dbSNP | Ensembl ].

VAR_002219

Natural variant

129

1

V → M in ADASCID; delayed-onset. Ref.31
Corresponds to variant rs121908731 [ dbSNP | Ensembl ].

VAR_002220

Natural variant

140

1

G → E in ADASCID. Ref.31
Corresponds to variant rs121908732 [ dbSNP | Ensembl ].

VAR_002221

Natural variant

142

1

R → Q in a pancreatic ductal adenocarcinoma sample; somatic mutation. Ref.28 Ref.33
Corresponds to variant rs61732239 [ dbSNP | Ensembl ].

VAR_002222

Natural variant

149

1

R → Q in ADASCID. Ref.19
Corresponds to variant rs121908737 [ dbSNP | Ensembl ].

VAR_002223

Natural variant

149

1

R → W in ADASCID. Ref.31
Corresponds to variant rs121908733 [ dbSNP | Ensembl ].

VAR_002224

Natural variant

152

1

L → M in an individual with partial ADA deficiency but no immunodeficiency; 1,5% of activity. Ref.30
Corresponds to variant rs121908728 [ dbSNP | Ensembl ].

VAR_002225

Natural variant

156

1

R → C in ADASCID. Ref.25
Corresponds to variant rs121908735 [ dbSNP | Ensembl ].

VAR_002226

Natural variant

156

1

R → H in ADASCID. Ref.26
Corresponds to variant rs121908722 [ dbSNP | Ensembl ].

VAR_002227

Natural variant

177

1

V → M in ADASCID; loss of activity. Ref.26
Corresponds to variant rs121908719 [ dbSNP | Ensembl ].

VAR_002228

Natural variant

179

1

A → D in ADASCID; loss of activity. Ref.29
Corresponds to variant rs121908727 [ dbSNP | Ensembl ].

VAR_002229

Natural variant

199

1

Q → P in ADASCID; delayed-onset. Ref.31
Corresponds to variant rs121908734 [ dbSNP | Ensembl ].

VAR_002230

Natural variant

211

1

R → C in ADASCID; late onset. Ref.19
Corresponds to variant rs121908740 [ dbSNP | Ensembl ].

VAR_002231

Natural variant

211

1

R → H in ADASCID. Ref.23
Corresponds to variant rs121908716 [ dbSNP | Ensembl ].

VAR_002232

Natural variant

215

1

A → T in ADASCID. Ref.19
Corresponds to variant rs114025668 [ dbSNP | Ensembl ].

VAR_002233

Natural variant

216

1

G → R in ADASCID; severe. Ref.26
Corresponds to variant rs121908723 [ dbSNP | Ensembl ].

VAR_002234

Natural variant

233

1

T → I in an individual with partial ADA deficiency but no immunodeficiency; 20% of activity. Ref.30
Corresponds to variant rs121908729 [ dbSNP | Ensembl ].

VAR_002235

Natural variant

274

1

P → L in ADASCID. Ref.19
Corresponds to variant rs121908738 [ dbSNP | Ensembl ].

VAR_002236

Natural variant

291

1

S → L in ADASCID. Ref.25 Ref.26
Corresponds to variant rs121908721 [ dbSNP | Ensembl ].

VAR_002237

Natural variant

297

1

P → Q in ADASCID. Ref.24
Corresponds to variant rs121908718 [ dbSNP | Ensembl ].

VAR_002238

Natural variant

304

1

L → R in ADASCID; loss of activity.

VAR_002239

Natural variant

329

1

A → V in ADASCID. Ref.23
Corresponds to variant rs121908715 [ dbSNP | Ensembl ].

VAR_002240

Natural variant

337

1

Missing in ADASCID.

VAR_002241

Experimental info

Sequence conflict

340

1

K → R in BAD97117. Ref.5

Secondary structure

1

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363

Helix Strand Turn

Details...

Beta strand

11 – 13

3

Helix

18 – 20

3

Helix

24 – 34

11

Helix

43 – 50

8

Helix

58 – 62

5

Helix

63 – 67

5

Helix

69 – 72

4

Helix

76 – 91

16

Turn

92 – 94

3

Beta strand

95 – 102

8

Helix

104 – 107

4

Beta strand

109 – 111

3

Helix

116 – 118

3

Helix

126 – 144

19

Beta strand

147 – 155

9

Helix

159 – 161

3

Helix

162 – 171

10

Turn

172 – 176

5

Beta strand

177 – 184

8

Helix

191 – 193

3

Helix

195 – 207

13

Beta strand

210 – 219

10

Helix

221 – 229

9

Beta strand

234 – 238

5

Helix

240 – 244

5

Helix

246 – 254

9

Beta strand

258 – 261

4

Helix

263 – 268

6

Beta strand

270 – 272

3

Helix

279 – 285

7

Beta strand

290 – 292

3

Helix

297 – 300

4

Helix

304 – 315

12

Helix

319 – 331

13

Beta strand

333 – 335

3

Helix

337 – 351

15

Helix

355 – 362

8

Sequences

	Sequence		Length	Mass (Da)
	P00813 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 786BC5085CA9AFCB	FASTA	363	40,764
	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

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 141-363.
[10]	"Direct association of adenosine deaminase with a T cell activation antigen, CD26." Kameoka J., Tanaka T., Nojima Y., Schlossman S.F., Morimoto C. Science 261:466-469(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DPP4, SUBCELLULAR LOCATION.
[11]	"Binding of adenosine deaminase to the lymphocyte surface via CD26." De Meester I., Vanham G., Kestens L., Vanhoof G., Bosmans E., Gigase P., Scharpe S. Eur. J. Immunol. 24:566-570(1994) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DPP4.
[12]	"Molecular characterization of dipeptidyl peptidase activity in serum: soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides." Durinx C., Lambeir A.M., Bosmans E., Falmagne J.B., Berghmans R., Haemers A., Scharpe S., De Meester I. Eur. J. Biochem. 267:5608-5613(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DPP4.
[13]	"Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase-CD26 interaction." Gines S., Marino M., Mallol J., Canela E.I., Morimoto C., Callebaut C., Hovanessian A., Casado V., Lluis C., Franco R. Biochem. J. 361:203-209(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]	"N-linked glycosylation of dipeptidyl peptidase IV (CD26): effects on enzyme activity, homodimer formation, and adenosine deaminase binding." Aertgeerts K., Ye S., Shi L., Prasad S.G., Witmer D., Chi E., Sang B.C., Wijnands R.A., Webb D.R., Swanson R.V. Protein Sci. 13:145-154(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APP4.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[16]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-54 AND LYS-232, MASS SPECTROMETRY.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"The crystal structure of human adenosine deaminase." Structural genomics consortium (SGC) Submitted (AUG-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 5-363 IN COMPLEX WITH NICKEL IONS AND 2-DEAOXYADENOSINE, COFACTOR.
[19]	"Hot spot mutations in adenosine deaminase deficiency." Hirschhorn R., Tzall S., Ellenbogen A. Proc. Natl. Acad. Sci. U.S.A. 87:6171-6175(1990) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID TRP-76; PRO-107; GLN-149; CYS-211; THR-215 AND LEU-274.
[20]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ADA*2 ASN-8.
[21]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID.
[22]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ADASCID GLN-101.
[23]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID TRP-101; HIS-211 AND VAL-329.
[24]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ADASCID GLN-297.
[25]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID CYS-156 AND LEU-291.
[26]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID LEU-101; HIS-156; MET-177; ARG-216 AND LEU-291.
[27]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ADASCID ARG-20.
[28]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-80 AND GLN-142.
[29]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID ASP-15; ASP-83 AND ASP-179.
[30]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS MET-152 AND ILE-233.
[31]	"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." Arrendondo-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) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ADASCID CYS-74; MET-129; GLU-140; TRP-149 AND PRO-199.
[32]	"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] [Europe PMC] [Abstract] Cited for: EFFECT OF VARIANT ADA*2 ASN-8 ON SLEEP.
[33]	"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses." Jones S., Zhang X., Parsons D.W., Lin J.C., Leary R.J., Angenendt P., Mankoo P., Carter H., Kamiyama H., Jimeno A., Hong S.M., Fu B., Lin M.T., Calhoun E.S., Kamiyama M., Walter K., Nikolskaya T., Nikolsky Y. , Hartigan J., Smith D.R., Hidalgo M., Leach S.D., Klein A.P., Jaffee E.M., Goggins M., Maitra A., Iacobuzio-Donahue C., Eshleman J.R., Kern S.E., Hruban R.H., Karchin R., Papadopoulos N., Parmigiani G., Vogelstein B., Velculescu V.E., Kinzler K.W. Science 321:1801-1806(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-142.
+	Additional computationally mapped references.

Web resources

ADAbase

ADA mutation db

GeneReviews

Wikipedia

Adenosine deaminase entry

Mendelian genes adenosine deaminase (ADA)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X02994 mRNA. Translation: CAA26734.1.
X02189 , 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.

IPI

IPI00296441.

PIR

DUHUA. A91032.

RefSeq

NP_000013.2. NM_000022.2.

UniGene

Hs.654536.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M7M	model	-	A	1-363	[»]
3IAR	X-ray	1.52	A	5-363	[»]

ProteinModelPortal

P00813.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-371N.

IntAct

P00813. 2 interactions.

MINT

MINT-5000852.

STRING

9606.ENSP00000361965.

PTM databases

PhosphoSite

P00813.

Polymorphism databases

DMDM

113339.

Proteomic databases

PaxDb

P00813.

PeptideAtlas

P00813.

PRIDE

P00813.

Protocols and materials databases

DNASU

100.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372874; ENSP00000361965; ENSG00000196839.

GeneID

100.

KEGG

hsa:100.

UCSC

uc002xmj.3. human.

Organism-specific databases

CTD

100.

GeneCards

GC20M043248.

HGNC

HGNC:186. ADA.

HPA

CAB004307.
HPA001399.
HPA023884.

MIM

102700. phenotype.
608958. gene.

neXtProt

NX_P00813.

Orphanet

39041. Omenn syndrome.
277. Severe combined immunodeficiency due to adenosine deaminase deficiency.

PharmGKB

PA24503.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1816.

HOGENOM

HOG000218816.

HOVERGEN

HBG001718.

InParanoid

P00813.

KO

K01488.

OMA

MPAIAGC.

OrthoDB

EOG40K808.

PhylomeDB

P00813.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02191-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00813.

SignaLink

P00813.

Gene expression databases

ArrayExpress

P00813.

Bgee

P00813.

CleanEx

HS_ADA.

Genevestigator

P00813.

GermOnline

ENSG00000196839. Homo sapiens.

Family and domain databases

InterPro

IPR006650. A/AMP_deam_AS.
IPR001365. A/AMP_deaminase_dom.
IPR006330. Ado/ade_deaminase.
[Graphical view]

Pfam

PF00962. A_deaminase. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01430. aden_deam. 1 hit.

PROSITE

PS00485. A_DEAMINASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00813.

ChEMBL

CHEMBL1910.

DrugBank

DB00640. Adenosine.
DB00242. Cladribine.
DB00975. Dipyridamole.
DB00199. Erythromycin.
DB01073. Fludarabine.
DB00249. Idoxuridine.
DB01280. Nelarabine.
DB00552. Pentostatin.
DB00277. Theophylline.
DB00194. Vidarabine.

EvolutionaryTrace

P00813.

GenomeRNAi

100.

NextBio

377.

SOURCE

Search...

Entry information

Entry name

ADA_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 166 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.