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Protein

Adenosine deaminase

Gene

Ada

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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: MGI
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase
    Biological processCell adhesion, Nucleotide metabolism
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.5.4.4 3474
    ReactomeiR-MMU-74217 Purine salvage
    SABIO-RKiP03958

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 2

    Organism-specific databases

    MGIiMGI:87916 Ada

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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-2DPAGEiP03958

    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 Expressed in 202 organ(s), highest expression level in esophagus
    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
    MINTiP03958
    STRINGi10090.ENSMUSP00000017841

    Chemistry databases

    BindingDBiP03958

    Structurei

    Secondary structure

    1352
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP03958
    SMRiP03958
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03958

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

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

    Family and domain databases

    CDDicd01320 ADA, 1 hit
    HAMAPiMF_00540 A_deaminase, 1 hit
    InterProiView protein in InterPro
    IPR006650 A/AMP_deam_AS
    IPR001365 A/AMP_deaminase_dom
    IPR028893 A_deaminase
    IPR006330 Ado/ade_deaminase
    IPR032466 Metal_Hydrolase
    PfamiView protein in Pfam
    PF00962 A_deaminase, 1 hit
    SUPFAMiSSF51556 SSF51556, 1 hit
    TIGRFAMsiTIGR01430 aden_deam, 1 hit
    PROSITEiView protein in PROSITE
    PS00485 A_DEAMINASE, 1 hit

    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

    Similar proteinsi

    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
    MINTiP03958
    STRINGi10090.ENSMUSP00000017841

    Chemistry databases

    BindingDBiP03958
    ChEMBLiCHEMBL3206

    PTM databases

    iPTMnetiP03958
    PhosphoSitePlusiP03958

    2D gel databases

    REPRODUCTION-2DPAGEiP03958

    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
    OMAiQWCGADR
    OrthoDBiEOG091G0NL8
    PhylomeDBiP03958
    TreeFamiTF314270

    Enzyme and pathway databases

    BRENDAi3.5.4.4 3474
    ReactomeiR-MMU-74217 Purine salvage
    SABIO-RKiP03958

    Miscellaneous databases

    ChiTaRSiAda mouse
    EvolutionaryTraceiP03958
    PROiPR:P03958
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000017697 Expressed in 202 organ(s), highest expression level in esophagus
    CleanExiMM_ADA
    ExpressionAtlasiP03958 baseline and differential
    GenevisibleiP03958 MM

    Family and domain databases

    CDDicd01320 ADA, 1 hit
    HAMAPiMF_00540 A_deaminase, 1 hit
    InterProiView protein in InterPro
    IPR006650 A/AMP_deam_AS
    IPR001365 A/AMP_deaminase_dom
    IPR028893 A_deaminase
    IPR006330 Ado/ade_deaminase
    IPR032466 Metal_Hydrolase
    PfamiView protein in Pfam
    PF00962 A_deaminase, 1 hit
    SUPFAMiSSF51556 SSF51556, 1 hit
    TIGRFAMsiTIGR01430 aden_deam, 1 hit
    PROSITEiView protein in PROSITE
    PS00485 A_DEAMINASE, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiADA_MOUSE
    AccessioniPrimary (citable) accession number: P03958
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 1986
    Last sequence update: January 23, 2007
    Last modified: October 10, 2018
    This is version 184 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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