Adenosine deaminase - Homo sapiens (Human)

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Names and origin

Protein names

Recommended name:
    Adenosine deaminase
    EC=3.5.4.4
Alternative name(s):
    Adenosine aminohydrolase

Gene names

Name:

ADA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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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.

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General annotation (Comments)

Catalytic activity	Adenosine + H(2)O = inosine + NH(3).
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. 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.

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Ontologies

Keywords
Biological process	Nucleotide metabolism
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary hemolytic anemia SCID
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	T cell activation Inferred from direct assay. Source: UniProtKB adenosine catabolic process Inferred from direct assay. Source: UniProtKB inosine biosynthetic process Inferred from direct assay. Source: MGI negative regulation of adenosine receptor signaling pathway Inferred from direct assay. Source: UniProtKB purine nucleotide salvage Inferred from mutant phenotype. 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. Source: UniProtKB response to hypoxia Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.13 Inferred from Experiment. Source: Reactome external side of plasma membrane Inferred from direct assay. Source: UniProtKB lysosome Inferred from direct assay. Source: UniProtKB
Molecular function	adenosine deaminase activity Ref.13 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB zinc ion binding Ref.19 Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

Removed

Chain

2 – 363

362

Adenosine deaminase

PRO_0000194352

Sites

Active site

214

1

Potential

Active site

262

1

Potential

Active site

295

1

Potential

Active site

296

1

Potential

Amino acid modifications

Modified residue

2

1

N-acetylalanine

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.

VAR_002209

Natural variant

15

1

H → D in ADASCID; loss of activity.

VAR_002210

Natural variant

20

1

G → R in ADASCID; loss of activity.

VAR_002211

Natural variant

74

1

G → C in ADASCID; delayed-onset.

VAR_002212

Natural variant

76

1

R → W in ADASCID.

VAR_002213

Natural variant

80

1

K → R

VAR_002214

Natural variant

83

1

A → D in ADASCID; loss of activity.

VAR_002215

Natural variant

101

1

R → L in ADASCID.

VAR_002216

Natural variant

101

1

R → Q in ADASCID; loss of activity.

VAR_002218

Natural variant

101

1

R → W in ADASCID.

VAR_002217

Natural variant

107

1

L → P in ADASCID.

VAR_002219

Natural variant

129

1

V → M in ADASCID; delayed-onset.

VAR_002220

Natural variant

140

1

G → E in ADASCID.

VAR_002221

Natural variant

142

1

R → Q in ADASCID; 20% of activity; ADA deficiency of late onset.

VAR_002222

Natural variant

149

1

R → Q in ADASCID.

VAR_002223

Natural variant

149

1

R → W in ADASCID.

VAR_002224

Natural variant

152

1

L → M in ADASCID; 1,5% of activity, partial ADA deficiency.

VAR_002225

Natural variant

156

1

R → C in ADASCID.

VAR_002226

Natural variant

156

1

R → H in ADASCID.

VAR_002227

Natural variant

177

1

V → M in ADASCID; loss of activity.

VAR_002228

Natural variant

179

1

A → D in ADASCID; loss of activity.

VAR_002229

Natural variant

199

1

Q → P in ADASCID; delayed-onset.

VAR_002230

Natural variant

211

1

R → C in ADASCID; late onset.

VAR_002231

Natural variant

211

1

R → H in ADASCID.

VAR_002232

Natural variant

215

1

A → T in ADASCID.

VAR_002233

Natural variant

216

1

G → R in ADASCID; severe.

VAR_002234

Natural variant

233

1

T → I in ADASCID; 20% of activity, partial ADA deficiency.

VAR_002235

Natural variant

274

1

P → L in ADASCID.

VAR_002236

Natural variant

291

1

S → L in ADASCID.

VAR_002237

Natural variant

297

1

P → Q in ADASCID.

VAR_002238

Natural variant

304

1

L → R in ADASCID; loss of activity.

VAR_002239

Natural variant

329

1

A → V in ADASCID.

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

.

363

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P00813-1 [UniParc].

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

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References

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[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.

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References