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P56658 (ADA_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenosine deaminase

EC=3.5.4.4
Alternative name(s):
Adenosine aminohydrolase
Gene names
Name:ADA
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length363 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. HAMAP-Rule MF_00540

Catalytic activity

Adenosine + H2O = inosine + NH3. HAMAP-Rule MF_00540

Cofactor

Binds 1 zinc ion per subunit.

Subunit structure

Interacts with DPP4 (extracellular domain) By similarity. Ref.5

Subcellular location

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. HAMAP-Rule MF_00540

Pharmaceutical use

Available under the name Adagen (Enzon). This is a PEG-conjugated form (pegademase). Used to treat patients with severe combined immunodeficiency diseases (SCID). HAMAP-Rule MF_00540

Sequence similarities

Belongs to the adenosine and AMP deaminases family.

Mass spectrometry

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

Ontologies

Keywords
   Biological processCell adhesion
Nucleotide metabolism
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoplasmic vesicle
Membrane
   Coding sequence diversityPolymorphism
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processT cell activation

Inferred from Biological aspect of Ancestor. Source: RefGenome

adenosine catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

hypoxanthine salvage

Inferred from Biological aspect of Ancestor. Source: RefGenome

inosine biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of adenosine receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleotide metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

purine ribonucleoside monophosphate biosynthetic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasmic membrane-bounded vesicle lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

external side of plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionadenosine deaminase activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DPP4P274875EBI-7475530,EBI-2871277From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2
Chain2 – 363362Adenosine deaminase HAMAP-Rule MF_00540
PRO_0000194351

Sites

Active site2171Proton donor Probable
Metal binding151Zinc; catalytic
Metal binding171Zinc; catalytic
Metal binding2141Zinc; catalytic
Metal binding2951Zinc; catalytic
Binding site171Substrate
Binding site191Substrate
Binding site1841Substrate; via amide nitrogen and carbonyl oxygen
Binding site2961Substrate
Site2381Important for catalytic activity

Amino acid modifications

Modified residue21N-acetylalanine HAMAP-Rule MF_00540
Modified residue541N6-acetyllysine By similarity
Modified residue2321N6-acetyllysine By similarity

Natural variations

Natural variant1991K → Q.
Natural variant2461A → T.
Natural variant3521G → R.

Experimental info

Sequence conflict81N → D AA sequence Ref.2
Sequence conflict32 – 332RK → KR AA sequence Ref.2
Sequence conflict571S → T AA sequence Ref.2
Sequence conflict601E → D AA sequence Ref.2
Sequence conflict77 – 793EAV → DAI AA sequence Ref.2
Sequence conflict2611V → I AA sequence Ref.2
Sequence conflict279 – 2813PVV → AVI AA sequence Ref.2
Sequence conflict313 – 3142NE → KD AA sequence Ref.2

Secondary structure

................................................................ 363
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P56658 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 69F6D25ACFF2A3E5

FASTA36340,919
        10         20         30         40         50         60 
MAQTPAFNKP KVELHVHLDG AIKPETILYY GRKRGIALPA DTPEELQNII GMDKPLSLPE 

        70         80         90        100        110        120 
FLAKFDYYMP AIAGCREAVK RIAYEFVEMK AKDGVVYVEV RYSPHLLANS KVEPIPWNQA 

       130        140        150        160        170        180 
EGDLTPDEVV SLVNQGLQEG ERDFGVKVRS ILCCMRHQPS WSSEVVELCK KYREQTVVAI 

       190        200        210        220        230        240 
DLAGDETIEG SSLFPGHVKA YAEAVKSGVH RTVHAGEVGS ANVVKEAVDT LKTERLGHGY 

       250        260        270        280        290        300 
HTLEDATLYN RLRQENMHFE VCPWSSYLTG AWKPDTEHPV VRFKNDQVNY SLNTDDPLIF 

       310        320        330        340        350        360 
KSTLDTDYQM TKNEMGFTEE EFKRLNINAA KSSFLPEDEK KELLDLLYKA YGMPSPASAE 


QCL 

« Hide

References

[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]"Primary structure of bovine adenosine deaminase."
Kelly M.A., Vestling M.M., Murphy C.M., Hua S., Sumpter T., Fenselau C.
J. Pharm. Biomed. Anal. 14:1513-1519(1996) [PubMed] [Europe PMC] [Abstract]
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]"Structural basis of compound recognition by adenosine deaminase."
Kinoshita T., Nakanishi I., Terasaka T., Kuno M., Seki N., Warizaya M., Matsumura H., Inoue T., Takano K., Adachi H., Mori Y., Fujii T.
Biochemistry 44:10562-10569(2005) [PubMed] [Europe PMC] [Abstract]
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF280603 mRNA. Translation: AAF91430.1.
RefSeqNP_776312.1. NM_173887.2.
UniGeneBt.4303.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KRMX-ray2.50A2-356[»]
1NDVX-ray2.30A2-356[»]
1NDWX-ray2.00A2-356[»]
1NDYX-ray2.00A2-356[»]
1NDZX-ray2.00A2-356[»]
1O5RX-ray2.35A2-356[»]
1QXLX-ray2.25A2-356[»]
1UMLX-ray2.50A2-356[»]
1V79X-ray2.50A2-356[»]
1V7AX-ray2.50A2-356[»]
1VFLX-ray1.80A2-356[»]
1W1IX-ray3.03E/F/G/H1-357[»]
1WXYX-ray2.50A2-356[»]
1WXZX-ray2.80A2-356[»]
2BGNX-ray3.15E/F/G/H2-362[»]
2E1WX-ray2.50A2-356[»]
2Z7GX-ray2.52A2-357[»]
ProteinModelPortalP56658.
SMRP56658. Positions 4-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP56658. 1 interaction.
STRING9913.ENSBTAP00000006947.

Chemistry

BindingDBP56658.
ChEMBLCHEMBL2966.
DrugBankDB00061. Pegademase bovine.

Proteomic databases

PaxDbP56658.
PRIDEP56658.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID280712.
KEGGbta:280712.

Organism-specific databases

CTD100.

Phylogenomic databases

eggNOGCOG1816.
HOGENOMHOG000218816.
HOVERGENHBG001718.
InParanoidP56658.
KOK01488.

Family and domain databases

HAMAPMF_00540. A_deaminase.
InterProIPR006650. A/AMP_deam_AS.
IPR001365. A/AMP_deaminase_dom.
IPR028893. A_deaminase.
IPR006330. Ado/ade_deaminase.
[Graphical view]
PfamPF00962. A_deaminase. 1 hit.
[Graphical view]
TIGRFAMsTIGR01430. aden_deam. 1 hit.
PROSITEPS00485. A_DEAMINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP56658.
NextBio20804891.

Entry information

Entry nameADA_BOVIN
AccessionPrimary (citable) accession number: P56658
Secondary accession number(s): Q9MYY1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 106 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references