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Protein

Adenosine deaminase

Gene

Ada

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:9272950). Plays an important role in purine metabolism and in adenosine homeostasis (PubMed:9272950, PubMed:10720488). Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events (PubMed:11435465). Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (By similarity). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (By similarity). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (By similarity). Stimulates plasminogen activation (By similarity). Plays a role in male fertility (By similarity). Plays a protective role in early postimplantation embryonic development (PubMed:9272950).By similarity3 Publications

Catalytic activityi

Adenosine + H2O = inosine + NH3.5 Publications

Cofactori

Zn2+3 PublicationsNote: Binds 1 zinc ion per subunit.3 Publications

Kineticsi

  1. KM=20 µM for adenosine2 Publications

    pH dependencei

    Optimum pH is 6-8.5.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi15Zinc; catalyticCombined sources4 Publications1
    Metal bindingi17Zinc; catalyticCombined sources4 Publications1
    Binding sitei17SubstrateCombined sources4 Publications1
    Binding sitei19SubstrateCombined sources4 Publications1
    Sitei58Important for interaction with adenosine receptors and increasing their affinity for agonistsBy similarity1
    Sitei62Important for interaction with adenosine receptors and increasing their affinity for agonistsBy similarity1
    Binding sitei184Substrate; via amide nitrogen and carbonyl oxygenCombined sources4 Publications1
    Metal bindingi214Zinc; catalyticCombined sources4 Publications1
    Active sitei217Proton donor2 Publications1
    Sitei238Important for catalytic activity2 Publications1
    Metal bindingi295Zinc; catalyticCombined sources4 Publications1
    Binding sitei296SubstrateCombined sources2 Publications1

    GO - Molecular functioni

    • adenosine deaminase activity Source: UniProtKB
    • purine nucleoside binding Source: Ensembl
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • adenosine catabolic process Source: UniProtKB
    • aging Source: Ensembl
    • dATP catabolic process Source: MGI
    • deoxyadenosine catabolic process Source: MGI
    • embryonic digestive tract development Source: MGI
    • germinal center B cell differentiation Source: MGI
    • histamine secretion Source: Ensembl
    • hypoxanthine biosynthetic process Source: MGI
    • hypoxanthine salvage Source: GO_Central
    • inosine biosynthetic process Source: UniProtKB
    • in utero embryonic development Source: MGI
    • liver development Source: MGI
    • lung alveolus development Source: MGI
    • lung development Source: MGI
    • negative regulation of adenosine receptor signaling pathway Source: MGI
    • negative regulation of apoptotic process Source: MGI
    • negative regulation of circadian sleep/wake cycle, non-REM sleep Source: Ensembl
    • negative regulation of inflammatory response Source: MGI
    • negative regulation of leukocyte migration Source: MGI
    • negative regulation of mature B cell apoptotic process Source: MGI
    • negative regulation of mucus secretion Source: MGI
    • negative regulation of penile erection Source: MGI
    • negative regulation of thymocyte apoptotic process Source: MGI
    • Peyer's patch development Source: MGI
    • placenta development Source: MGI
    • positive regulation of alpha-beta T cell differentiation Source: MGI
    • positive regulation of B cell proliferation Source: MGI
    • positive regulation of calcium-mediated signaling Source: MGI
    • positive regulation of germinal center formation Source: MGI
    • positive regulation of heart rate Source: MGI
    • positive regulation of smooth muscle contraction Source: MGI
    • positive regulation of T cell activation Source: MGI
    • positive regulation of T cell differentiation Source: MGI
    • positive regulation of T cell differentiation in thymus Source: MGI
    • positive regulation of T cell receptor signaling pathway Source: MGI
    • purine nucleotide salvage Source: MGI
    • purine ribonucleoside monophosphate biosynthetic process Source: InterPro
    • regulation of cell-cell adhesion mediated by integrin Source: MGI
    • regulation of T cell differentiation Source: MGI
    • response to drug Source: Ensembl
    • response to hydrogen peroxide Source: Ensembl
    • response to hypoxia Source: MGI
    • response to morphine Source: Ensembl
    • response to vitamin E Source: Ensembl
    • T cell activation Source: MGI
    • trophectodermal cell differentiation Source: MGI
    • xanthine biosynthetic process Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Cell adhesion, Nucleotide metabolism

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.5.4.4. 3474.
    ReactomeiR-MMU-74217. Purine salvage.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Adenosine deaminase (EC:3.5.4.45 Publications)
    Alternative name(s):
    Adenosine aminohydrolase
    Gene namesi
    Name:Ada
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 2

    Organism-specific databases

    MGIiMGI:87916. Ada.

    Subcellular locationi

    • Cell membrane By similarity; Peripheral membrane protein By similarity; Extracellular side By similarity
    • Cell junction By similarity
    • Cytoplasmic vesicle lumen 1 Publication
    • Cytoplasm By similarity
    • Lysosome By similarity

    • Note: Colocalized with DPP4 at the cell surface.By similarity

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Lysosome, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Lethal at perinatal stages. Fetuses are viable up to 18 dpc, but after this survival decreases rapidly. Fewer that 10% of mutant pups are born live, and these die within hours after birth. Mutant fetuses display much higher than normal levels of adenosine and dATP, respiratory distress, hepatocellular degeneration and necrosis. Prenatal lethality can be avoided using an ADA expression vector with a trophoblast-specific promoter. Mutant mice die after about three weeks due to immunodeficiency, disturbances in purine metabolism and severe lung inflammation.3 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi217E → D: Reduces catalytic activity 700-fold. No effect on affinity for adenosine. 1 Publication1
    Mutagenesisi217E → G: Reduces catalytic activity 3200-fold. No effect on affinity for adenosine. 1 Publication1
    Mutagenesisi217E → Q: Reduces catalytic activity 4800-fold, and slighly increases affinity for substrate. 1 Publication1
    Mutagenesisi217E → S: Loss of activity. 1 Publication1
    Mutagenesisi238H → A: Increases affinity for adenosine 20-fold. Reduces enzyme activity 500-fold. 1 Publication1
    Mutagenesisi238H → E: Nearly abolishes enzyme activity. 1 Publication1
    Mutagenesisi238H → R: Reduces enzyme activity 1500-fold. No effect on affinity for adenosine. 1 Publication1
    Mutagenesisi295D → E: No effect on affinity for adenosine. Reduces enzyme activity 2750-fold. 1 Publication1
    Mutagenesisi296D → A: Reduces affinity for adenosine 70-fold. Reduces enzyme activity 110000-fold. 1 Publication1
    Mutagenesisi296D → N: Reduces affinity for adenosine 10-fold. Reduces enzyme activity 100-fold. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL3206.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedBy similarity
    ChainiPRO_00001943532 – 352Adenosine deaminaseAdd BLAST351

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylalanineBy similarity1
    Modified residuei54N6-acetyllysineBy similarity1
    Modified residuei232N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiP03958.
    PaxDbiP03958.
    PeptideAtlasiP03958.
    PRIDEiP03958.

    2D gel databases

    REPRODUCTION-2DPAGEP03958.

    PTM databases

    iPTMnetiP03958.
    PhosphoSitePlusiP03958.

    Expressioni

    Tissue specificityi

    Detected in brain neurons in the median emninence (at protein level) (PubMed:8783262). Expressed in secondary deciduum (at protein level) (PubMed:9272950). Found in all tissues, occurs in large amounts in T-lymphocytes and, at the time of weaning, in gastrointestinal tissues.2 Publications

    Developmental stagei

    Expressed in trophoblast at 7.5 dpc and 9.5 dpc.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000017697.
    CleanExiMM_ADA.
    ExpressionAtlasiP03958. baseline and differential.
    GenevisibleiP03958. MM.

    Interactioni

    Subunit structurei

    Interacts with DPP4 (via extracellular domain). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4.By similarity

    Protein-protein interaction databases

    IntActiP03958. 2 interactors.
    MINTiMINT-4087128.
    STRINGi10090.ENSMUSP00000017841.

    Chemistry databases

    BindingDBiP03958.

    Structurei

    Secondary structure

    1352
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi11 – 13Combined sources3
    Helixi18 – 20Combined sources3
    Helixi24 – 34Combined sources11
    Helixi43 – 50Combined sources8
    Helixi58 – 62Combined sources5
    Helixi65 – 72Combined sources8
    Helixi76 – 92Combined sources17
    Beta strandi95 – 102Combined sources8
    Helixi105 – 107Combined sources3
    Beta strandi109 – 111Combined sources3
    Helixi116 – 118Combined sources3
    Helixi126 – 144Combined sources19
    Beta strandi147 – 155Combined sources9
    Helixi159 – 161Combined sources3
    Helixi162 – 171Combined sources10
    Turni174 – 176Combined sources3
    Beta strandi177 – 184Combined sources8
    Helixi191 – 193Combined sources3
    Helixi195 – 207Combined sources13
    Beta strandi210 – 219Combined sources10
    Helixi221 – 229Combined sources9
    Beta strandi234 – 238Combined sources5
    Helixi240 – 244Combined sources5
    Helixi246 – 254Combined sources9
    Beta strandi258 – 261Combined sources4
    Helixi263 – 268Combined sources6
    Beta strandi270 – 272Combined sources3
    Helixi279 – 285Combined sources7
    Beta strandi289 – 292Combined sources4
    Helixi297 – 300Combined sources4
    Helixi304 – 315Combined sources12
    Helixi319 – 332Combined sources14
    Beta strandi333 – 335Combined sources3
    Helixi337 – 350Combined sources14

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1A4LX-ray2.60A/B/C/D4-352[»]
    1A4MX-ray1.95A/B/C/D4-352[»]
    1ADDX-ray2.40A4-352[»]
    1FKWX-ray2.40A4-352[»]
    1FKXX-ray2.40A4-352[»]
    1UIOX-ray2.40A4-352[»]
    1UIPX-ray2.40A4-352[»]
    2ADAX-ray2.40A1-352[»]
    3KM8X-ray2.00A/B1-352[»]
    3MVIX-ray1.60A/B4-352[»]
    3MVTX-ray2.20A/C4-352[»]
    3T1GX-ray2.35A4-352[»]
    ProteinModelPortaliP03958.
    SMRiP03958.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03958.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG1097. Eukaryota.
    COG1816. LUCA.
    GeneTreeiENSGT00730000111151.
    HOGENOMiHOG000218816.
    HOVERGENiHBG001718.
    InParanoidiP03958.
    KOiK01488.
    OMAiMPAIAGC.
    OrthoDBiEOG091G0NL8.
    PhylomeDBiP03958.
    TreeFamiTF314270.

    Family and domain databases

    CDDicd01320. ADA. 1 hit.
    HAMAPiMF_00540. A_deaminase. 1 hit.
    InterProiIPR006650. A/AMP_deam_AS.
    IPR001365. A/AMP_deaminase_dom.
    IPR028893. A_deaminase.
    IPR006330. Ado/ade_deaminase.
    IPR032466. Metal_Hydrolase.
    [Graphical view]
    PfamiPF00962. A_deaminase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51556. SSF51556. 1 hit.
    TIGRFAMsiTIGR01430. aden_deam. 1 hit.
    PROSITEiPS00485. A_DEAMINASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P03958-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAQTPAFNKP KVELHVHLDG AIKPETILYF GKKRGIALPA DTVEELRNII
    60 70 80 90 100
    GMDKPLSLPG FLAKFDYYMP VIAGCREAIK RIAYEFVEMK AKEGVVYVEV
    110 120 130 140 150
    RYSPHLLANS KVDPMPWNQT EGDVTPDDVV DLVNQGLQEG EQAFGIKVRS
    160 170 180 190 200
    ILCCMRHQPS WSLEVLELCK KYNQKTVVAM DLAGDETIEG SSLFPGHVEA
    210 220 230 240 250
    YEGAVKNGIH RTVHAGEVGS PEVVREAVDI LKTERVGHGY HTIEDEALYN
    260 270 280 290 300
    RLLKENMHFE VCPWSSYLTG AWDPKTTHAV VRFKNDKANY SLNTDDPLIF
    310 320 330 340 350
    KSTLDTDYQM TKKDMGFTEE EFKRLNINAA KSSFLPEEEK KELLERLYRE

    YQ
    Length:352
    Mass (Da):39,992
    Last modified:January 23, 2007 - v3
    Checksum:iE53A8A1FABA148CD
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti141E → R in AAB07142 (PubMed:2387582).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M10319 mRNA. Translation: AAA37173.1.
    M34251
    , M34242, M34243, M34244, M34246, M34247, M34248, M34249, M34250 Genomic DNA. Translation: AAB07142.1.
    U73107 Genomic DNA. Translation: AAC08442.1.
    AF483480 mRNA. Translation: AAL90754.1.
    AF483481 mRNA. Translation: AAL90755.1.
    AK075899 mRNA. Translation: BAC36039.1.
    BC002075 mRNA. Translation: AAH02075.1.
    CCDSiCCDS17015.1.
    PIRiA01010. DUMSA.
    RefSeqiNP_001258981.1. NM_001272052.1.
    NP_031424.1. NM_007398.4.
    UniGeneiMm.388.

    Genome annotation databases

    EnsembliENSMUST00000017841; ENSMUSP00000017841; ENSMUSG00000017697.
    GeneIDi11486.
    KEGGimmu:11486.
    UCSCiuc008ntl.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M10319 mRNA. Translation: AAA37173.1.
    M34251
    , M34242, M34243, M34244, M34246, M34247, M34248, M34249, M34250 Genomic DNA. Translation: AAB07142.1.
    U73107 Genomic DNA. Translation: AAC08442.1.
    AF483480 mRNA. Translation: AAL90754.1.
    AF483481 mRNA. Translation: AAL90755.1.
    AK075899 mRNA. Translation: BAC36039.1.
    BC002075 mRNA. Translation: AAH02075.1.
    CCDSiCCDS17015.1.
    PIRiA01010. DUMSA.
    RefSeqiNP_001258981.1. NM_001272052.1.
    NP_031424.1. NM_007398.4.
    UniGeneiMm.388.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1A4LX-ray2.60A/B/C/D4-352[»]
    1A4MX-ray1.95A/B/C/D4-352[»]
    1ADDX-ray2.40A4-352[»]
    1FKWX-ray2.40A4-352[»]
    1FKXX-ray2.40A4-352[»]
    1UIOX-ray2.40A4-352[»]
    1UIPX-ray2.40A4-352[»]
    2ADAX-ray2.40A1-352[»]
    3KM8X-ray2.00A/B1-352[»]
    3MVIX-ray1.60A/B4-352[»]
    3MVTX-ray2.20A/C4-352[»]
    3T1GX-ray2.35A4-352[»]
    ProteinModelPortaliP03958.
    SMRiP03958.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiP03958. 2 interactors.
    MINTiMINT-4087128.
    STRINGi10090.ENSMUSP00000017841.

    Chemistry databases

    BindingDBiP03958.
    ChEMBLiCHEMBL3206.

    PTM databases

    iPTMnetiP03958.
    PhosphoSitePlusiP03958.

    2D gel databases

    REPRODUCTION-2DPAGEP03958.

    Proteomic databases

    EPDiP03958.
    PaxDbiP03958.
    PeptideAtlasiP03958.
    PRIDEiP03958.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000017841; ENSMUSP00000017841; ENSMUSG00000017697.
    GeneIDi11486.
    KEGGimmu:11486.
    UCSCiuc008ntl.2. mouse.

    Organism-specific databases

    CTDi100.
    MGIiMGI:87916. Ada.

    Phylogenomic databases

    eggNOGiKOG1097. Eukaryota.
    COG1816. LUCA.
    GeneTreeiENSGT00730000111151.
    HOGENOMiHOG000218816.
    HOVERGENiHBG001718.
    InParanoidiP03958.
    KOiK01488.
    OMAiMPAIAGC.
    OrthoDBiEOG091G0NL8.
    PhylomeDBiP03958.
    TreeFamiTF314270.

    Enzyme and pathway databases

    BRENDAi3.5.4.4. 3474.
    ReactomeiR-MMU-74217. Purine salvage.

    Miscellaneous databases

    ChiTaRSiAda. mouse.
    EvolutionaryTraceiP03958.
    PROiP03958.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000017697.
    CleanExiMM_ADA.
    ExpressionAtlasiP03958. baseline and differential.
    GenevisibleiP03958. MM.

    Family and domain databases

    CDDicd01320. ADA. 1 hit.
    HAMAPiMF_00540. A_deaminase. 1 hit.
    InterProiIPR006650. A/AMP_deam_AS.
    IPR001365. A/AMP_deaminase_dom.
    IPR028893. A_deaminase.
    IPR006330. Ado/ade_deaminase.
    IPR032466. Metal_Hydrolase.
    [Graphical view]
    PfamiPF00962. A_deaminase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51556. SSF51556. 1 hit.
    TIGRFAMsiTIGR01430. aden_deam. 1 hit.
    PROSITEiPS00485. A_DEAMINASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiADA_MOUSE
    AccessioniPrimary (citable) accession number: P03958
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 23, 1986
    Last sequence update: January 23, 2007
    Last modified: November 30, 2016
    This is version 172 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.