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P56658

- ADA_BOVIN

UniProt

P56658 - ADA_BOVIN

Protein

Adenosine deaminase

Gene

ADA

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    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 By similarity.By similarity

    Catalytic activityi

    Adenosine + H2O = inosine + NH3.

    Cofactori

    Binds 1 zinc ion per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi15 – 151Zinc; catalytic
    Metal bindingi17 – 171Zinc; catalytic
    Binding sitei17 – 171Substrate
    Binding sitei19 – 191Substrate
    Binding sitei184 – 1841Substrate; via amide nitrogen and carbonyl oxygen
    Metal bindingi214 – 2141Zinc; catalytic
    Active sitei217 – 2171Proton donorCurated
    Sitei238 – 2381Important for catalytic activity
    Metal bindingi295 – 2951Zinc; catalytic
    Binding sitei296 – 2961Substrate

    GO - Molecular functioni

    1. adenosine deaminase activity Source: UniProtKB
    2. protein binding Source: IntAct
    3. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. adenosine catabolic process Source: UniProtKB
    2. cell adhesion Source: UniProtKB-KW
    3. hypoxanthine salvage Source: RefGenome
    4. inosine biosynthetic process Source: UniProtKB
    5. negative regulation of adenosine receptor signaling pathway Source: RefGenome
    6. nucleotide metabolic process Source: UniProtKB-KW
    7. purine ribonucleoside monophosphate biosynthetic process Source: InterPro
    8. T cell activation Source: RefGenome

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Cell adhesion, Nucleotide metabolism

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Adenosine deaminase (EC:3.5.4.4)
    Alternative name(s):
    Adenosine aminohydrolase
    Gene namesi
    Name:ADA
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Unplaced

    Subcellular locationi

    Cell membrane By similarity; Peripheral membrane protein By similarity; Extracellular side By similarity. Cell junction By similarity. Cytoplasmic vesicle lumen By similarity. Cytoplasm By similarity
    Note: Colocalized with DPP4 at the cell junction in lymphocyte-epithelial cell adhesion.By similarity

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-SubCell
    2. cytoplasmic membrane-bounded vesicle lumen Source: UniProtKB-SubCell
    3. cytosol Source: RefGenome
    4. external side of plasma membrane Source: RefGenome

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Pharmaceutical usei

    Available under the name Adagen (Enzon). This is a PEG-conjugated form (pegademase). Used to treat patients with severe combined immunodeficiency diseases (SCID).

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 363362Adenosine deaminasePRO_0000194351Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine
    Modified residuei54 – 541N6-acetyllysineBy similarity
    Modified residuei232 – 2321N6-acetyllysineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP56658.
    PRIDEiP56658.

    Interactioni

    Subunit structurei

    Interacts with DPP4 (extracellular domain).By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DPP4P274875EBI-7475530,EBI-2871277From a different organism.

    Protein-protein interaction databases

    IntActiP56658. 1 interaction.
    STRINGi9913.ENSBTAP00000006947.

    Structurei

    Secondary structure

    1
    363
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi11 – 133
    Helixi18 – 203
    Helixi24 – 3310
    Helixi43 – 508
    Helixi58 – 7215
    Helixi76 – 9217
    Beta strandi95 – 1028
    Helixi105 – 1073
    Beta strandi109 – 1113
    Helixi116 – 1183
    Helixi126 – 14419
    Beta strandi147 – 1559
    Helixi159 – 1613
    Helixi162 – 17110
    Turni174 – 1763
    Beta strandi177 – 1848
    Helixi191 – 1933
    Helixi195 – 20713
    Beta strandi210 – 21910
    Helixi221 – 2299
    Beta strandi234 – 2385
    Helixi240 – 2445
    Helixi246 – 2549
    Beta strandi258 – 2614
    Helixi263 – 2697
    Beta strandi270 – 2723
    Helixi279 – 2857
    Beta strandi289 – 2924
    Helixi297 – 3004
    Helixi304 – 31310
    Helixi319 – 33113
    Beta strandi333 – 3353
    Helixi337 – 35115

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1KRMX-ray2.50A2-357[»]
    1NDVX-ray2.30A2-357[»]
    1NDWX-ray2.00A2-357[»]
    1NDYX-ray2.00A2-357[»]
    1NDZX-ray2.00A2-357[»]
    1O5RX-ray2.35A2-357[»]
    1QXLX-ray2.25A2-357[»]
    1UMLX-ray2.50A2-357[»]
    1V79X-ray2.50A2-357[»]
    1V7AX-ray2.50A2-357[»]
    1VFLX-ray1.80A2-357[»]
    1W1IX-ray3.03E/F/G/H1-357[»]
    1WXYX-ray2.50A2-357[»]
    1WXZX-ray2.80A2-357[»]
    2BGNX-ray3.15E/F/G/H2-363[»]
    2E1WX-ray2.50A2-357[»]
    2Z7GX-ray2.52A2-357[»]
    ProteinModelPortaliP56658.
    SMRiP56658. Positions 4-351.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP56658.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG1816.
    HOGENOMiHOG000218816.
    HOVERGENiHBG001718.
    InParanoidiP56658.
    KOiK01488.

    Family and domain databases

    HAMAPiMF_00540. A_deaminase.
    InterProiIPR006650. A/AMP_deam_AS.
    IPR001365. A/AMP_deaminase_dom.
    IPR028893. A_deaminase.
    IPR006330. Ado/ade_deaminase.
    [Graphical view]
    PfamiPF00962. A_deaminase. 1 hit.
    [Graphical view]
    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.

    P56658-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAQTPAFNKP KVELHVHLDG AIKPETILYY GRKRGIALPA DTPEELQNII    50
    GMDKPLSLPE FLAKFDYYMP AIAGCREAVK RIAYEFVEMK AKDGVVYVEV 100
    RYSPHLLANS KVEPIPWNQA EGDLTPDEVV SLVNQGLQEG ERDFGVKVRS 150
    ILCCMRHQPS WSSEVVELCK KYREQTVVAI DLAGDETIEG SSLFPGHVKA 200
    YAEAVKSGVH RTVHAGEVGS ANVVKEAVDT LKTERLGHGY HTLEDATLYN 250
    RLRQENMHFE VCPWSSYLTG AWKPDTEHPV VRFKNDQVNY SLNTDDPLIF 300
    KSTLDTDYQM TKNEMGFTEE EFKRLNINAA KSSFLPEDEK KELLDLLYKA 350
    YGMPSPASAE QCL 363
    Length:363
    Mass (Da):40,919
    Last modified:January 23, 2007 - v3
    Checksum:i69F6D25ACFF2A3E5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81N → D AA sequence (PubMed:8877857)Curated
    Sequence conflicti32 – 332RK → KR AA sequence (PubMed:8877857)Curated
    Sequence conflicti57 – 571S → T AA sequence (PubMed:8877857)Curated
    Sequence conflicti60 – 601E → D AA sequence (PubMed:8877857)Curated
    Sequence conflicti77 – 793EAV → DAI AA sequence (PubMed:8877857)Curated
    Sequence conflicti261 – 2611V → I AA sequence (PubMed:8877857)Curated
    Sequence conflicti279 – 2813PVV → AVI AA sequence (PubMed:8877857)Curated
    Sequence conflicti313 – 3142NE → KD AA sequence (PubMed:8877857)Curated

    Mass spectrometryi

    Molecular mass is 40549±16 Da from positions 2 - 363. Determined by ESI. 1 Publication

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti199 – 1991K → Q.
    Natural varianti246 – 2461A → T.
    Natural varianti352 – 3521G → R.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF280603 mRNA. Translation: AAF91430.1.
    RefSeqiNP_776312.1. NM_173887.2.
    UniGeneiBt.4303.

    Genome annotation databases

    GeneIDi280712.
    KEGGibta:280712.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Worthington enzyme manual

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF280603 mRNA. Translation: AAF91430.1 .
    RefSeqi NP_776312.1. NM_173887.2.
    UniGenei Bt.4303.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1KRM X-ray 2.50 A 2-357 [» ]
    1NDV X-ray 2.30 A 2-357 [» ]
    1NDW X-ray 2.00 A 2-357 [» ]
    1NDY X-ray 2.00 A 2-357 [» ]
    1NDZ X-ray 2.00 A 2-357 [» ]
    1O5R X-ray 2.35 A 2-357 [» ]
    1QXL X-ray 2.25 A 2-357 [» ]
    1UML X-ray 2.50 A 2-357 [» ]
    1V79 X-ray 2.50 A 2-357 [» ]
    1V7A X-ray 2.50 A 2-357 [» ]
    1VFL X-ray 1.80 A 2-357 [» ]
    1W1I X-ray 3.03 E/F/G/H 1-357 [» ]
    1WXY X-ray 2.50 A 2-357 [» ]
    1WXZ X-ray 2.80 A 2-357 [» ]
    2BGN X-ray 3.15 E/F/G/H 2-363 [» ]
    2E1W X-ray 2.50 A 2-357 [» ]
    2Z7G X-ray 2.52 A 2-357 [» ]
    ProteinModelPortali P56658.
    SMRi P56658. Positions 4-351.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P56658. 1 interaction.
    STRINGi 9913.ENSBTAP00000006947.

    Chemistry

    BindingDBi P56658.
    ChEMBLi CHEMBL2966.
    DrugBanki DB00061. Pegademase bovine.

    Proteomic databases

    PaxDbi P56658.
    PRIDEi P56658.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 280712.
    KEGGi bta:280712.

    Organism-specific databases

    CTDi 100.

    Phylogenomic databases

    eggNOGi COG1816.
    HOGENOMi HOG000218816.
    HOVERGENi HBG001718.
    InParanoidi P56658.
    KOi K01488.

    Miscellaneous databases

    EvolutionaryTracei P56658.
    NextBioi 20804891.

    Family and domain databases

    HAMAPi MF_00540. A_deaminase.
    InterProi IPR006650. A/AMP_deam_AS.
    IPR001365. A/AMP_deaminase_dom.
    IPR028893. A_deaminase.
    IPR006330. Ado/ade_deaminase.
    [Graphical view ]
    Pfami PF00962. A_deaminase. 1 hit.
    [Graphical view ]
    TIGRFAMsi TIGR01430. aden_deam. 1 hit.
    PROSITEi PS00485. A_DEAMINASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The binding site of human adenosine deaminase for CD26/dipeptidyl peptidase IV: the Arg142Gln mutation impairs binding to CD26 but does not cause immune deficiency."
      Richard E., Arredondo-Vega F.X., Santisteban I., Kelly S.J., Patel D.D., Hershfield M.S.
      J. Exp. Med. 192:1223-1236(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: PROTEIN SEQUENCE OF 2-357, MASS SPECTROMETRY.
    3. "Structure of bovine adenosine deaminase complexed with 6-hydroxy-1,6-dihydropurine riboside."
      Kinoshita T., Nishio N., Nakanishi I., Sato A., Fujii T.
      Acta Crystallogr. D 59:299-303(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-356 IN COMPLEX WITH ZINC IONS AND TRANSITION STATE ANALOG 6-HYDROXY-1,6-DIHYDROPURINE RIBOSIDE.
    4. "A highly potent non-nucleoside adenosine deaminase inhibitor: efficient drug discovery by intentional lead hybridization."
      Terasaka T., Kinoshita T., Kuno M., Nakanishi I.
      J. Am. Chem. Soc. 126:34-35(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-356 IN COMPLEX WITH INHIBITOR AND ZINC IONS.
    5. "Crystal structure of CD26/dipeptidyl-peptidase IV in complex with adenosine deaminase reveals a highly amphiphilic interface."
      Weihofen W.A., Liu J., Reutter W., Saenger W., Fan H.
      J. Biol. Chem. 279:43330-43335(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.03 ANGSTROMS) OF 1-357 IN COMPLEX WITH ZINC IONS AND DPP4, SUBUNIT.
    6. "Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors."
      Terasaka T., Okumura H., Tsuji K., Kato T., Nakanishi I., Kinoshita T., Kato Y., Kuno M., Seki N., Naoe Y., Inoue T., Tanaka K., Nakamura K.
      J. Med. Chem. 47:2728-2731(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-356 IN COMPLEX WITH INHIBITOR.
    7. "Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors."
      Terasaka T., Kinoshita T., Kuno M., Seki N., Tanaka K., Nakanishi I.
      J. Med. Chem. 47:3730-3743(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 2-356 IN COMPLEX WITH INHIBITOR.
    8. Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-356 IN COMPLEX WITH INHIBITOR.
    9. "Crystal structures of HIV-1 Tat-derived nonapeptides Tat-(1-9) and Trp2-Tat-(1-9) bound to the active site of dipeptidyl-peptidase IV (CD26)."
      Weihofen W.A., Liu J., Reutter W., Saenger W., Fan H.
      J. Biol. Chem. 280:14911-14917(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) OF 2-362 IN COMPLEX WITH DPP4 AND A HIV-1 TAT PEPTIDE.
    10. "Rational design of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors: predicting enzyme conformational change and metabolism."
      Terasaka T., Tsuji K., Kato T., Nakanishi I., Kinoshita T., Kato Y., Kuno M., Inoue T., Tanaka K., Nakamura K.
      J. Med. Chem. 48:4750-4753(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-356 IN COMPLEX WITH INHIBITOR AND ZINC IONS.
    11. "Conformational change of adenosine deaminase during ligand-exchange in a crystal."
      Kinoshita T., Tada T., Nakanishi I.
      Biochem. Biophys. Res. Commun. 373:53-57(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 2-357 IN COMPLEX WITH EHNA.

    Entry informationi

    Entry nameiADA_BOVIN
    AccessioniPrimary (citable) accession number: P56658
    Secondary accession number(s): Q9MYY1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 109 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, Direct protein sequencing, Pharmaceutical, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3