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P56658

- ADA_BOVIN

UniProt

P56658 - ADA_BOVIN

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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).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. 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
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 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-KW
  2. cytoplasmic vesicle Source: UniProtKB-KW
  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).

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 – 133Combined sources
Helixi18 – 203Combined sources
Helixi24 – 3310Combined sources
Helixi43 – 508Combined sources
Helixi58 – 7215Combined sources
Helixi76 – 9217Combined sources
Beta strandi95 – 1028Combined sources
Helixi105 – 1073Combined sources
Beta strandi109 – 1113Combined sources
Helixi116 – 1183Combined sources
Helixi126 – 14419Combined sources
Beta strandi147 – 1559Combined sources
Helixi159 – 1613Combined sources
Helixi162 – 17110Combined sources
Turni174 – 1763Combined sources
Beta strandi177 – 1848Combined sources
Helixi191 – 1933Combined sources
Helixi195 – 20713Combined sources
Beta strandi210 – 21910Combined sources
Helixi221 – 2299Combined sources
Beta strandi234 – 2385Combined sources
Helixi240 – 2445Combined sources
Helixi246 – 2549Combined sources
Beta strandi258 – 2614Combined sources
Helixi263 – 2697Combined sources
Beta strandi270 – 2723Combined sources
Helixi279 – 2857Combined sources
Beta strandi289 – 2924Combined sources
Helixi297 – 3004Combined sources
Helixi304 – 31310Combined sources
Helixi319 – 33113Combined sources
Beta strandi333 – 3353Combined sources
Helixi337 – 35115Combined sources

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

        10         20         30         40         50
MAQTPAFNKP KVELHVHLDG AIKPETILYY GRKRGIALPA DTPEELQNII
60 70 80 90 100
GMDKPLSLPE FLAKFDYYMP AIAGCREAVK RIAYEFVEMK AKDGVVYVEV
110 120 130 140 150
RYSPHLLANS KVEPIPWNQA EGDLTPDEVV SLVNQGLQEG ERDFGVKVRS
160 170 180 190 200
ILCCMRHQPS WSSEVVELCK KYREQTVVAI DLAGDETIEG SSLFPGHVKA
210 220 230 240 250
YAEAVKSGVH RTVHAGEVGS ANVVKEAVDT LKTERLGHGY HTLEDATLYN
260 270 280 290 300
RLRQENMHFE VCPWSSYLTG AWKPDTEHPV VRFKNDQVNY SLNTDDPLIF
310 320 330 340 350
KSTLDTDYQM TKNEMGFTEE EFKRLNINAA KSSFLPEDEK KELLDLLYKA
360
YGMPSPASAE QCL
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.

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 29, 2014
This is version 110 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