SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P56658

- ADA_BOVIN

UniProt

P56658 - ADA_BOVIN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein
Adenosine deaminase
Gene
ADA
Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.UniRule annotation

Catalytic activityi

Adenosine + H2O = inosine + NH3.UniRule annotation

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 donor Inferred
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
Complete GO annotation...

GO - Biological processi

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

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; Peripheral membrane protein; 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.UniRule annotation

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
Complete GO annotation...

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).UniRule annotation

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 363362Adenosine deaminaseUniRule annotation
PRO_0000194351Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineUniRule annotation
Modified residuei54 – 541N6-acetyllysine By similarity
Modified residuei232 – 2321N6-acetyllysine By similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP56658.
PRIDEiP56658.

Interactioni

Subunit structurei

Interacts with DPP4 (extracellular domain) By similarity.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

IntActiP56658. 1 interaction.
STRINGi9913.ENSBTAP00000006947.

Structurei

Secondary structure

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.

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

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti8 – 81N → D AA sequence 1 Publication
Sequence conflicti32 – 332RK → KR AA sequence 1 Publication
Sequence conflicti57 – 571S → T AA sequence 1 Publication
Sequence conflicti60 – 601E → D AA sequence 1 Publication
Sequence conflicti77 – 793EAV → DAI AA sequence 1 Publication
Sequence conflicti261 – 2611V → I AA sequence 1 Publication
Sequence conflicti279 – 2813PVV → AVI AA sequence 1 Publication
Sequence conflicti313 – 3142NE → KD AA sequence 1 Publication

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...

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: July 9, 2014
This is version 108 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

Similar proteinsi